In order to explore the degree of association between negative life events and depression in the college student population, and to reveal the potential influence mechanism of depression in college students, the Adolescent Life Events Scale (ASLEC), the Self-Depression Scale (SDS), the Social Support Scale (SSRS), and the Resilience Scale for Adolescent Mental Health (RSCA) were selected as the survey tools, and a questionnaire survey was carried out on 633 college students, and on the A theoretical model with mediating and moderating effects was constructed on this basis. The results of the study showed that: (1) college students' depressive symptoms as a whole were in the controllable range; (2) negative life events, social support, and psychological resilience were significantly associated with depression (|r|=0.144-0.555, p<0.01); (3) negative life events significantly and positively predicted the depression (β=0.53, p<0.01); and (4) mental toughness had a significant moderating effect in the pathway of negative life events predicting depression (t = 2.914, p<0.01). The study suggests that negative life events indirectly exacerbate depression by weakening social support, while mental toughness enhances the protective effect of social support. Colleges and universities should focus on developing students' psychological coping skills and providing effective social support to better prevent and alleviate depressive symptoms among college students.