The current academic research on entrepreneurship focuses on the entrepreneurial intention and opportunity identification and utilization of entrepreneurs in the early stage of entrepreneurship, as well as the entrepreneurial performance and entrepreneurial results after the establishment of entrepreneurial enterprises. Few studies focus on the entrepreneurial persistence of entrepreneurs in the development stage of entrepreneurial enterprises. Entrepreneurial persistence enables entrepreneurs to stick to their goals in adversity and continue to carry out positive entrepreneurial behaviors, which is conducive to the survival and development of enterprises and improves the chances of entrepreneurial success. Entrepreneurial persistence plays an important role in the entire process of entrepreneurship. Based on self-regulation theory, social cognition theory and emotional contagion theory, this study’s purpose and objective is to construct a theoretical model of the mechanism of entrepreneurial passion on entrepreneurial persistence with entrepreneurial self-efficacy and work vitality as mediating variables and emotional intelligence as moderating variables. The process of cognitive strengthening and emotional activation realizes the transformation from entrepreneurial passion to entrepreneurial persistence. The quantitative empirical research was carried out by obtaining data through a questionnaire survey. Both theoretical models and empirical analysis show that entrepreneurial passion can improve entrepreneurial persistence through entrepreneurial self-efficacy and work vitality, and emotional intelligence plays an important role in regulating it. This study also confirmed the moderating mediation model of entrepreneurial passion and entrepreneurial persistence.