What is the relevance of the title 'Of Mice and Men' to the novel?
It is from a Robert Burns poem, "The best laid schemes of mice and men go often askew". In the case of the story, Lennie and George and Candy have a plan. They're going to finally save enough and go in together to buy a house with a little land. They get to escape the fear of "getting canned", Lennie gets to "tend dem rabbits" and Candy can live out his years in relative security.
But of course, that's not what happens. Before they can put their plan in motion, Lennie accidentally kills Curley's wife, escapes, the posse goes after him, and George is forced to make a horrible choice. Their best laid plans had definitely gone askew.
In addition to the relation to the Robert Burns's poem explained above, there is also a kind of symmetry in the novella explained through the title. In Chapter 1, Lennie kills the mouse because he becomes a little over-zealous in his desire to pet something soft. Near the end of the novella we see the same basic plot line with Curley's wife. When she encourages Lennie to feel how soft her hair is, we know instantly what will happen next. In essence, the fate of the mouse and the fate of Curley's wife--like the puppy, the often mentioned rabbits, and even Lennie himself--are one in the same.