BackgroundBoth internet addiction (IA) and non-suicidal self-injury (NSSI) are major public health concerns among adolescents, however, the association between IA and NSSI was not well understood. We aimed to investigate the association between IA and NSSI within a cohort study, and explore the mediated effect of depressive symptoms and the moderating effect of social support in the association.MethodsA total of 1530 adolescents aged 11–14 years who completed both the baseline (T1) and 14-month follow-up (T2) survey of the Chinese Adolescent Health Growth Cohort were included for the current analysis. IA, NSSI, depressive symptoms and social support were measured at T1; depressive symptoms and NSSI were measured again at T2. Structural equation models were employed to estimate the mediated effect of depressive symptoms and the moderating effect of social support in the association between IA and NSSI at T2.ResultsIA was independently associated with an increased risk of NSSI at T2, with the total effect of 0.113 (95%CI 0.055–0.174). Depressive symptoms mediated the association between IA and NSSI at T2, and social support moderated the indirect but not the direct effect of IA on NSSI at T2. Sex differences were found on the mediated effect of depressive symptoms and the moderated mediation effect of social support.ConclusionsInterventions that target adolescents’ NSSI who also struggle with IA may need to focus on reducing depressive symptoms and elevating social support.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12888-023-04754-4.