Consider that the key themes of this novel are violence, isolation, dealing with loss, and racism. Alexie uses humor, therefore, to soften to seriousness of the book as a whole, and to make the narrator and main character likable and memorable.
In the novel, Junior details graphic experiences of being bullied, not just from his peers, but from adults on the reservation as well. His own best friend beats him up. Through these accounts, an entire culture of physical violence is portrayed. The best example of this is Rowdy, his violent nature, and the fact that his own father beats him severely. Junior experiences violence as a regular and almost daily occurrence. And he is ostracized because of his differences to a degree that most people will never experience in life. These are two very difficult themes to swallow, especially through the eyes and experience of a young boy.
Additionally, Junior goes through more loss in a very short period of his childhood than most people experience in a lifetime. From the terrible death of his dog (due to poverty and the fact that they could not afford a vet), to his grandmother being hit by a drunk driver, to his dad's best friend being shot in the face, to his sister dying in a trailer fire, Junior is inundated with several deaths all in a short period of time. And these aren't the kind of deaths we are used to hearing about, like dying of cancer or a heart attack. They are all basically freak accidents. Not ironically, the majority of the deaths detailed in the novel are either a direct or an indirect result of drunkenness. So yet another ugly truth of Native American life is revealed.
And finally, the entire book is riddled with the racism that exists between Native Americans and white people. This is probably demonstrated best at the various portrayals of basketball games, that, even at a high school level, are taken far more seriously than they should be. The entire town shows up. Parents boo and catcall from the stands. Junior is physically assaulted by someone in the audience. He is ostracized, again, in his life, but this time it is for becoming a traitor. The deep seeded resentment between Indians and white people is alive and modernized in this book, and it is yet another difficult reality to hear from the mind and mouth of a young kid.
While this book might not be directly auto-biographical, Alexie admitted later that it is definitely a portrait of reservation life, in all its ugliness. This Native American author knew that revealing these truths to the white world would be an enormous cultural shock. Therefore, he chooses a narrator who balances the heaviness of his circumstances with a very adult-level of humor. In doing this, the author successfully taps into several emotions all at the same time. On one hand, the reader is devastated and almost as angry as Junior about the things he's experiencing, but in the midst of it, laughing at Junior's sardonic responses.
This book had an immediate following when it was published, received lots of attention and awards, and continues to be widely read and studied, because of this balance of humor, with the heavy and ugly reality of a culture so many Americans perhaps previously never knew about. And though Junior and his experiences are so different from typical American teenage lives, through this narrator and his humor, Alexie successfully portrays universal human emotions, thereby bridging the cultural gaps between his characters and his audience.