To investigate the influence of proactive personality on the process and difficulties of college students’ career decision-making, a questionnaire survey was conducted with 1540 college students. The results showed that (1) proactive personality significantly and negatively predicts college students’ career decision-making difficulties; (2) perceived social support moderates the relationship between proactive personality and college students’ career decision-making difficulties; (3) career decision-making self-efficacy mediates the influence of the interaction term between proactive personality and perceived social support on college students’ career decision-making difficulties. The practical implications of this study are discussed