Starting from various problems existing in college students' innovation and entrepreneurship activities, this paper explores the similarities between craftsman spirit and innovation and entrepreneurship ability, analyzes the significance of their combination for social development, and puts forward the integration of craftsman spirit and innovation and entrepreneurship in theoretical teaching, innovation and entrepreneurship practice and psychological teaching. And through some specific methods to achieve the relevant theory, improve the talent training system in colleges and universities, cultivate students' "artisan spirit", and enhance the ability of innovation and entrepreneurship.