To explore the influencing and protective factors of depression among college students and identify the mediating pathways of negative life events, social support, and psychological resilience on depression, this study conducted a questionnaire survey on 633 college students using psychological scales and tested the proposed hypotheses using a moderated mediation model. The findings revealed that, ① overall, depression among current college students is within a manageable range. ② Negative life events, social support, and psychological resilience were significantly correlated with depression. ③Negative life events positively predicted depression while social support partially mediated this relationship (effect size=0.069, P<0.01). ④Psychological resilience significantly moderated the effect of negative life events on depression (β=0.093, P<0.01). These findings validate the applicability of the Diathesis-Stress Model and Buffer Theory of Social Support among college students, revealing that negative life events indirectly exacerbate depression by weakening social support, while psychological resilience strengthens the protective effect of social support. Higher education institutions should prioritize cultivating students' psychological coping capacities, providing effective social support, and addressing the needs of students with moderate to severe depression through targeted intervention and counseling.