College students face pressure from various aspects such as academics, employment, and interpersonal relationships, and their mental health is receiving increasing attention. This study used a cross-sectional, descriptive correlational design to recruit 842 college students to explore the relationship between self-compassion and psychological flourishing and the underlying psychological mechanisms. With gender added as a control variable, the results showed the following: (1) self-compassion had a positive predictive effect on psychological flourishing in college students; (2) hope partially mediated the predictive effect of self-compassion on psychological flourishing in college students; (3) the first half path of the mediation model was moderated by emotion regulation. In conclusion, this study revealed the underlying mechanisms of the association between self-compassion and psychological flourishing. The mechanisms of increasing college students’ psychological flourishing are the positive impact of hope on the relationship of self-compassion and psychological flourishing, and emotional regulation enhancing the impact of hope. These findings not only enrich the theoretical framework of the relationship between self-compassion and psychological flourishing but also provide practical guidance for future applications of mindfulness and compassion skills to promote physical and mental health. Future research could further explore the effectiveness of self-compassion interventions in different populations, and how cultivating mindfulness and compassion skills can increase individuals’ levels of self-compassion, thereby promoting mental health and overall well-being.