Of Mice and Men is a tragic book because the characters are victims of fate, and are destroyed by forces outside their control.
Of Mice and Men is the story of two men, George and Lennie, who travel together. Lennie is mentally challenged, so George looks out for him. This is the first tragedy. George is saddled with Lennie, because if he leaves him Lennie would never survive alone. The tragic part is that George cannot live his own life because he is always looking after Lennie.
Lennie’s condition makes him a tragic figure because he cannot control his own actions. George is a tragic figure because he is trying to live with factors outside his control. When Lennie kills Curley’s wife, George has to shoot Lennie even though he is his best friend, because Lennie would be caught and punished, and because it is not safe to leave Lennie where he might hurt others.
"A guy got to sometimes." But Carlson was standing over George. "How'd you do it?" he asked. "I just done it," George said tiredly. (ch 6)
In essence, the book is the story what happens when two tragic figures succumb to fate. George kills Lennie because he has to.