Miss Lonelyhearts is Nathanael West's second novel. It is an Expressionist black comedy set in New York City during the Great Depression.

In the story, Miss Lonelyhearts is an unnamed male newspaper columnist writing an advice column, which is viewed by the newspaper as a joke. As "Miss Lonelyhearts" reads letters from desperate New Yorkers, he feels terribly burdened and falls into a cycle of deep depression, accompanied by heavy drinking and occasional barfights. He also suffers from the pranks and cynical advice of his editor at the newspaper, named "Shrike", which is also a type of predatory bird. Miss Lonelyhearts tries several approaches as a way out of this depression (including religion, escaping to the countryside, and sex) but only ends up more confused.

The general theme of the novel is one of extreme disillusionment with Depression-era American society, a consistent theme throughout West's novels. However, the novel is essentially a black comedy and is characterized by an extremely dark but clever sense of humor and irony. The novel can be treated as a meditation on the theme of theodicy, or the problem of why evil exists in the world. The novel's protagonist is psychologically overwhelmed by his perception of this evil, which is treated as an explanation for his increasingly desperate psychological condition. Although the characters of Miss Lonelyhearts are grotesque caricatures, the periodic letters sent to Miss Lonelyhearts, which describe real people with real insoluble problems, serve to ground the novel's Expressionism in reality.