Objective To investigate the effect of negative life events on non-suicidal self-injury in adolescents with depressive disorder, and the mediating role of perceived social support and rumination on the relationship between negative life events and non-suicidal self-injury. Methods From August 2022 to November 2022, 394 adolescent patients with depressive disorder who were treated in the psychiatry department of a tertiary hospital in Wuhan were selected as the research objects. A questionnaire survey was conducted with the support scale and the rumination scale. All data processing and analysis were performed using SPSS 26.0, and correlation analysis, Bootstrap analysis, etc. were used to test the mediation effect. Results Negative life events directly affected non-suicidal self-injury(P＜0.001), the direct effect accounted for 68.99％ of the total effect, and was partially mediated by comprehension of social support, partly mediated by rumination, and the chain of comprehension of social support and rumination. The mediating effect affects non-suicidal self-injury, and the mediating effect accounts for 6.20％, 21.71％, and 3.10％ of the total effect, respectively. Conclusion Negative life event injury can directly affect the non-suicidal self-injury behavior of adolescents with depressive disorder, and it can also indirectly affect nonsuicidal self-injury through comprehension of social support and rumination.