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In a nutshell, he tells him to stay away from his wife, only known in the novel as Curley's wife. Curley is excessively protective of his wife and suspicious and jealous of anyone who tries to interact with her in any way. When Lennie expresses to George that he thinks Curley's wife is "pretty", George realizes that Lennie may get in trouble by showing any interest at all in Curley's wife, so he wants to assure that Lennie doesn't interact with her. In addition, George feels it is best that he stays out of Curley's way because Lennie often tends to unintentionally get in trouble whenever he opens his mouth.
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