IntroductionNon-suicidal self-injury (NSSI) is highly prevalent in depression, and is associated with psychosocial factors, emotion dysregulation, and strategies of cognitive emotion regulation. However, the internal combination and interactions of these risk factors in depression remain unclear.MethodsData from 122 patients with depression, including 56 with NSSI and 66 without NSSI, were analyzed. Self-rating scales were used to assess psychosocial factors, emotion dysregulation, and cognitive regulation strategies. Sparse partial least squares discriminant analysis (sPLS-DA) was employed to explore internal combinations in each profile. A moderated mediation model was applied to examine their interactional relationship.ResultsThe results identified an NSSI-related psychosocial profile characterized by high neuroticism, childhood trauma, poor family functioning, and low psychological resilience. Emotion dysregulation, including high levels of alexithymia, anhedonia, and emotion regulation difficulties, mediated the association between this psychosocial profile and NSSI. The mediated effect was further moderated by maladaptive cognitive regulation strategies.LimitationsLack of sufficient information on NSSI frequency and severity. Relatively small sample size for discussing the impact of gender and age of depressive patients with NSSI.ConclusionThese findings hold important implications for the prevention, treatment, and rehabilitation of NSSI.