Objective:To explore the mediating effect of self-esteem and resilience,and the moderating role of left-behind experience on negative life events and depression in college students.Methods:Totally 879 college students were selected from 3 universities in Sichuan and Chongqing (396 college students with left-behind experience,483 college students without left-behind experience).The Adolescent Self-Rating Life Events Check List (ASLEC),Self-esteem Scale (SES),Resilience Scale of Chinese Adolescent (RSCA) and Self-Rating Depression Scale (SDS) were used to measure the negative life events,self-esteem,resilience and depression.The Bootstrap program and multiple-group analysis were used to test mediation effect and moderation effect.Results:Scores of ASLEC were higher in those with left-behind experience than in those without left-behind experience [(9.0 ± 3.8)vs.(6.8 ± 3.1),P ＜ 0.001].College students'left-behind experience was positively correlated with scores of ASLEC and SDS (r ＝0.22-0.22,Ps ＜0.01),while negatively correlated with scores of RSCA and SES (r ＝-0.29--0.56,Ps ＜0.01).The complete mediating effect of the scores of SES and RSCA between ASLEC score and SDS score was significant (mediating effect ＝ 0.08,0.13,0.07;Ps ＜ 0.01).It was significant that the mediaring roles of self-esteem and resilience (95％ CI:0.13-0.68).Left-behind experience played the moderating effect on self-esteem and resilience (the constraint model fitting degree of variation was △x2 ＝ 2120.68,△df＝ 8,P ＜ 0.001).Conclusions:Self-esteem and resilience completely mediates college students'negative events and depression,which is moderated by their previous left-behind experience.