INTRODUCTION: Adolescents with mood disorders are at an exceptionally high risk for non-suicidal self-injury (NSSI); however, the understanding of the core factors underlying this vulnerability remains limited. This knowledge gap significantly hampers the effectiveness of targeted prevention and intervention strategies. METHODS: A total of 263 adolescents with mood disorders completed a series of self-report surveys, covering demographic, personal, and social factors related to NSSI. We first used least absolute shrinkage and selection operator (LASSO) regression to identify the core related factors. Then, we employed network analysis to construct the network structure of these core factors. RESULTS: Our findings indicate that depressive and anxiety symptoms are the strongest influencing factors for NSSI among adolescents with mood disorders. Life events and the specific functions of NSSI are identified as personalized factors within this group. Additionally, objective social support and education level emerged as potential protective factors against NSSI. These factors are not independent but interact with each other. CONCLUSION: By identifying and intervening in these key factors, more effective prevention strategies and personalized treatment plans can be developed, ultimately improving the quality of life and psychological well-being of adolescents with mood disorders.