The major irony in Of Mice and Men is that George kills Lennie because of their friendship. George kills Lennie to spare him from a worse death. George complained about Lennie and his defects, but realizes his importance only after his death. Once Lennie is dead, George loses the weight of responsibility Lennie caused him, but he is also lonely. Also, Lennie and George's dream to own their own farm that is carried out throughout the novel dissapears with Lennie's death.
George and Lennie dream of owning a little farm of ten acres with a windmill, a little shack, an orchard and many animals. The dream keeps them going and makes their work easier but also solidifies their friendship. The dream that leads them on will die with Lennie's death. The dream of Lennie and George is one of the types of American Dream popular in American fiction. Their dream is that of wealth and land, the desire for a home, and to work their own land.
For Lennie in particular it is to have responsibility for once, to look after the rabbits, and to finally have a sense of self worth. Yet the irony in Of Mice and Men is that the dream seems a mirage, it will not be achieved. George and Lennie try to deny their social class and role in the world, but the outcome will prove this dream to be unreachable. George and Lennie only own their arms and the friendship between them.
Lennie's retardation causes irony in the novel. Despite the fact that Lennie is fundamentally good, a grown child, he harms those that surround him. This can be seen when he kills the mouse because he stroked it too hard. Yet, the killing of the mouse was caused by his affection for it,