Hazel is a 16-year-old girl with cancer, which she calls a "side effect of dying" (p.3). Another side effect of dying, according to Hazel, is her depression, and though she sees this as normal and incurable, her mother talks to one of her many doctors and gets her set up with antidepressants and a regularly meeting support group for youths with cancer. Hazel tells the reader about herself and her diagnosis through her interactions at Support Group - she introduces herself each meeting along with the fact that she has thyroid cancer that has spread to her lungs, always saying that she's "okay." She doesn't like anyone in the group, including the leader Patrick who once had testicular cancer, besides a teenage boy named Isaac who lost his eye to cancer and may be losing another.
One week not too long after joining the support group, Hazel attends one week - pausing to explain to the reader that she must take certain supporting technologies with her everywhere, namely an oxygen tank attached to a cannula that delivers oxygen directly to her nostrils - to find a hot boy, new to the group, staring at her. He is Isaac’s friend, introduced to the group as Augustus, and Hazel decides not to be threatened by his stare but to stare back at him until he looks away first. She succeeds, and when Patrick asks Augustus for his diagnosis (osteosarcoma a year and a half before) and about his fears (to which Augustus responds "oblivion" (p.12)), Hazel makes a speech about lack of meaning to which Augustus responds "Goddamn...aren't you something else" (p.13).
After Support Group, Isaac, Augustus, and Hazel talk together. When Isaac leaves, Augustus and Hazel continue talking; he calls her beautiful and compares her to Natalie Portman in V for Vendetta. He invites her over to his house to watch the movie, which she doesn't immediately accept. They walk outside, Hazel noticing his prosthetic leg, and share mutual disgust over Isaac and his girlfriend Monica making out aggressively against the church wall. Augustus takes out a cigarette and Hazel is immediately enraged, calling it is hamartia or fatal flaw and berating him with disappointment. Augustus explains that he never lights them, only enjoying them for the feeling of putting something that could kill him between his lips but not giving it the power to do so. Intrigued, Hazel tells her mom (who has come to get her) that she will be watching a movie with Augustus.
Augustus drives Hazel to his house - a bumpy and terrifying ride because of his prosthetic leg. He and Hazel discuss "Cancer Perks" - items and allowances that young people with cancer get because of people's pity or sympathy for them. He asks Hazel about her story with cancer, and we learn more about Hazel's journey over the past three years. She had surgery, radiation, and chemotherapy, but her tumors continued to grow and her lungs started to fill with liquid. At one point, her "miracle," her lungs were very full and she had pneumonia that wasn't responding to antibiotics and her doctors and parents thought she would definitely die then. However, her "Cancer Doctor," Dr. Maria, was able to get fluid out of her lungs and put her on a new cancer drug called Phalanxifor, which shrank her tumors. Hazel is now able to live at home and take classes at community college, though is still saddled with her oxygen tank, medical check-ups, and fatigue since the cancer is not gone but only kept at bay.
Hazel meets Augustus's parents and Augustus tells them that they will be watching a movie downstairs, to which his parents respond that they will be watching the movie in the living room. Augustus does manage to show her downstairs, and down there they discuss his prior basketball prowess, as evidenced by a collection of trophies. He tells her that just before he had his leg amputated he decided that games like that are silly and pointless when you think about them more critically. He asks her about her life outside of cancer and they talk about poetry and literature. Hazel decides to tell him about her favorite book, An Imperial Affliction, and he says that he'll read it if she'll read his favorite, The Price of Dawn. They watch V for Vendetta in Augustus's living room, which is adorned with "Encouragements" such as "Without pain, how could we know joy?" (P.35.) Augustus drives her home and asks to see her again, to which she replies that she'll call him when she finishes his book, knowing his phone number will be written inside it.
Hazel stays up late reading his book; her mom, who usually lets her sleep in because "sleep fights cancer" (p.38) wakes her up to get her excited about her half-birthday (Hazel's mother, who has stopped working to care for Hazel full-time tries to keep their lives happy and exciting by celebrating holidays with pizzazz). She encourages Hazel to contact her friend Kaitlyn and they make plans. After class, Hazel's mom drives her to the mall where she buys the two sequels to Augustus's book and then meets Kaitlyn. They shop for shoes together, though the situations is made awkward when Kaitlyn blanches after making a joke relating to death, though Hazel downplays it lightly with a joke of her own. Hazel soon craves alone time and pleads tiredness to end her time with Kaitlyn, retreating to a quiet part of the mall to read her new books. While reading, a little girl approaches Hazel who asks questions about her cannula; though the little girls mother calls to her disapprovingly, Hazel likes the little girl and the encounter.
Before bed that night, Hazel begins to re-read An Imperial Affliction yet again. The book is about a young girl named Anna who has cancer but instead of starting a charity for cancer creates one for finding a cure for cholera. The book ends in the middle of a sentence, which Hazel understands as an artistic choice to demonstrate the abruptness of death or illness worsening, but still wishes to know the end to. However, the book's author Peter Van Houten has since moved from America to Amsterdam and lives seemingly reclusively, having produced no further literary work. Hazel calls Augustus and they talk briefly, but she flirtatiously tells him that he can't see her until he finishes the book. The next day, after class and a movie with her mom, Hazel sees she has received a lot of messages from Augustus despairing about the non-ending of the book. She calls him and hears noises in the background "like the death cry of some injured animal" which turn out to be coming from Isaac. Augustus invites her over to his house to visit both of them.
Isaac and Augustus are playing the video game version of The Price of Dawn, but Isaac is crying heavily. His girlfriend Monica, who so often repeated their word "always" back to him, has broken up with him before rather than after his eye operation after which he will be completely blind. Isaac becomes unsatisfied getting out his rage through the video game and turns to destroying Augustus's room; Augustus allows him to destroy his entire basketball trophy collection after which Isaac says he does not feel better but evidently has gotten the anger out of his system for the time being.
After this "Night of Broken Trophies," Hazel does not hear from Augustus for about a week. She becomes worried, and after a quick dinner one night she calls him. Augustus says he's been waiting to call her until he has collected his thoughts about An Imperial Affliction. He talks to her about the book and its author briefly, lingering on the fact that he is apparently unreachable. Augustus then reveals that he has reached him, through his assistant, and gotten a full email from him. Hazel is flabbergasted, thinking this is the "best gift ever," and writes her own email to send to Peter Van Houten with her questions about what happens after the end of the book. After writing the email, she calls Augustus back and they talk at length. They transition from talking about books to talking about kissing, and Augustus reveals that he previously had a girlfriend who died. They decide they have to get off the phone, but not before establishing a word like a more guarded version of Isaac and Monica's "always" - "okay" (p.73).
A few days later, Hazel receives a text from Augustus saying that Isaac is now blind but NEC (no evidence of cancer). Hazel drives to see Isaac at the hospital where they talk about Monica not having visited him and about the qualities of good and bad nurses. She buys him flowers, leaving them with his mom.
The next morning, Hazel finds an email reply from Peter Van Houten saying that he does not trust any form of technological communication to transmit what happens after the story ends, but that if she ever finds herself in Amsterdam she should visit him. She tells the news to her mom, who seems tentatively willing to help her go, but realizing their money situation Hazel says that she will find a way to go to Amsterdam without her parents having to pay. She calls Augustus and they talk about The Genie Foundation, which gives children with cancer each a "Wish," though Hazel admits that she used hers to go to Disney World when she was 13.
That weekend, Hazel and her parents go to the farmers' market and while there Hazel gets a call from Gus saying that he will be waiting at her house when she gets back. He brings her bright orange flowers and asks her parents to take her on a secret date. He takes her to the sculpture garden behind the art museum where a large skeleton sculpture called Funky Bones is on display. He reveals that this sculpture is by a Dutch artist, that the jersey he is wearing as a Dutch basketball player, and that orange - the color of her flowers along with all of the food he has brought for a picnic - is the national color of the Netherlands. He gives a speech to her, witty and sweet yet not allowing for actual conversation, revealing that he has made it his "Wish" to take her to Amsterdam to meet Peter Van Houten. They almost kiss, but Hazel flinches at the last moment and the chapter ends with her simply telling him that he's the best.
Hazel begins the story with a description of her lack of agency - told by her mother that she has depression, forced to go to Support Group and then to speak there, even given depression and cancer itself by the fact of death. Though lack of agency is a main theme in the book, it does not mean that Hazel and the characters do not do anything. Green writes a complex enough character that Hazel keeps an active life seeing friends, taking classes, and spending time with her family, and caring about books and television shows even though it is clear that she sometimes feels forced into these actions when they seem pointless in the larger scheme of life.
In quick succession, the reader is shown Hazel's relationships with her mother, Kaitlyn, Augustus, and a brief encounter with the young girl at the mall. These relationships demonstrate the difficulty of love and friendship for someone with an illness or hardship. To have a relationship, one must - like the little girl and unlike Kaitlyn - not be so afraid of offending the person that you shy away from making a real connection with them or validating and taking interest in their feelings. However, what Augustus and Hazel's mother are able to do is recognize and care about her cancer but also look past it to her interests and happiness.
The parallel romance story of Isaac and Monica, over almost as quickly as it is introduced, ironically foils the relationship that develops between Hazel and Augustus. Isaac and Monica seem unafraid of getting hurt, Isaac believing that true love will allow them to persevere, and is unprepared when the blow comes rather than the perhaps over-preparation Hazel attempts, as will be shown further in the coming chapters. Hazel, demonstrating an incredible ability to empathize, understands both Isaac and Monica's points of view, telling Isaac that is wasn't nice to or for her either, his having cancer and losing his eyes. This shock of reality does not heal Isaac's wounds, but it gives perspective to both him and the reader on the lack of antagonist and antagonism Hazel sees in characters and in cancer itself.
Three characters' parents are shown in the book - Hazel's mother and father, Augustus's mother and father, and Isaac's mother. The parents as a group are fairly homogeneous, with none of them divorced or in financial duress, perhaps one thing overlooked by Green in his focus on portraying the lives of teens coping with illness or potentially simply a representation of the parents of children who would end up receiving care in similar areas and choosing to spend time together. Hazel and Augustus's parents are lightly contrasted, with Augustus's relying more on religion and faith in pleasant sayings. Parents are quite important to the story, however, as one of Hazel's main concerns is not hurting her parents further financially while living or emotionally when she dies.
An Imperial Affliction is in parallel to The Fault in Our Stars as books about cancer but not "cancer-books" in that they do not over-glorify the fight against cancer or show a martyred young cancer-sufferer who founds a charity. Instead, both books deal honestly with a young girl who has cancer and is looking to live life apart from only having cancer and potentially do some good. This parallel will be important later when looking at the connection between a book and its author and subject (in relation to Green's own writing of this book). Hazel and Augustus's reactions to the end of the book are also symbolic, with Hazel wanting desperately what happens after the book ends in a way that defies her knowledge of the book as a work of art and literature and betrays her youthful desire for answers and perhaps meaning after life.