Objective To explore the mediating role of depression between internat addiction and selfinjury among left-behind adolescents and the regulatory role of social support. Methods Using the stratified cluster sampling method， 1 945 left-behind students were selected from 8 township junior high schools in a county of Chongqing from September to December 2019 as the research objects. The online questionnaire survey was conducted with the Diagnostic Scale of Internet Addiction for Middle School Students， Self-Injury Scale， Patients' Health Questionnaire Depression Scale-9 Item and Adolescent Social Support Rating Scale. Pearson correlation and point two column correlation were used to analyze the correlation between internet addiction and depression， social support and self-injury among left-behind adolescents. PROCESS V4.0 was applied to analyze the mediation effect of depression between internet addiction and self-injury among left-behind adolescents and the regulatory effect of social support. Results The detection rate of self-injury among left-behind adolescents was 31.8% （619/1 945）. They were divided into self-injury group （n=619） and non-self-injury group （n=1 326） according to whether they have self-injury behavior. There was a statistically significant difference between the two groups of left-behind adolescents （χ2 =4.153， P＜ 0.05）. Correlation analysis showed that internet addiction was positively correlated with depression and self-injury， and negatively correlated with social support； depression was positively correlated with self-injury （r=0.314，0.307，-0.203，0.371； P ＜ 0.01）. Mediating effect analysis showed that depression played a partially mediating role between internet addiction and selfinjury. The standardized mediating effect of depression was 0.11， which accounted for 31.4% of the total effect. Moderating effect analysis showed that the relationship between internet addiction and depression was moderated by social support（β=-0.162， P＜ 0.01）. Conclusions There is a mediating effect between internet addiction and self-injury among left-behind adolescents. Depression is the intermediary variable of the relationship between the two. Social support buffered the impact of internet addiction on depression. The higher the level of social support， the weaker the impact of internet addiction on depression.