BACKGROUND: This study aimed to examine the impact of stressful life events on the depressive symptoms of Chinese first-year university students, while considering the influence of interpersonal relationships and gender on this association. METHODS: A total of 8079 first-year Chinese university students were surveyed using the Adolescent Self-Rating Life Events Check List (ASLEC), Beck Depression Inventory (BDI), and Comprehensive Diagnostic Scale of Interpersonal Relationship (CDSIR). RESULTS: Stressful life event were positively correlated with interpersonal relationships, depressive symptoms, and gender (r = 0.385, 0.264, 0.055, p < 0.001); there was a significant positive correlation between depressive symptoms and interpersonal relationships (r = 0.473, p < 0.001). Stressful life events partially predict depressive symptoms through the mediation of interpersonal relationships, and the proportion of indirect total effect was 63.26 %. The effect of stressful life events on depressive symptoms was moderated by gender. Stressful life events had a positive effect on depressive symptoms in both male and female individuals. Compared with male individuals (simple slope = 0.070, t = 3.467, p < 0.001), female individuals were more susceptible to stressful life events (simple slope = 0.185, t = 9.652, p < 0.001). LIMITATIONS: The generalizability of the findings is constrained by the composition of the sample. The study's utilization of questionnaire methodology and cross-sectional design poses limitations in establishing definitive causality. CONCLUSION: The effect of stressful life events on depressive symptoms might be mediated by interpersonal relationships and moderated by gender.