<p>Non-suicidal self-injury (NSSI) is a prominent mental health issue among adolescents. Cumulative ecological risk, defined as concurrent stressors across family, school, and peer systems, has been identified as a key risk factor. However, the underlying mechanisms and protective factors in this relationship have not been fully explored. This study explores the longitudinal relationship between cumulative ecological risk and NSSI, focusing on the serial mediating roles of self-compassion and depressive symptoms, as well as the moderating role of positive stress beliefs. Participants were 742 Chinese adolescents (52.7% female; Mage at Wave 1 = 13.4 years) from a two-wave longitudinal study with data spanning 1 year. Results indicated that cumulative ecological risk indirectly influenced NSSI through the sequential pathway of self-compassion followed by depressive symptoms. Furthermore, positive stress beliefs functioned as a conditional protective factor: they amplified the protective effect of self-compassion on NSSI, and they attenuated the positive association between depressive symptoms and NSSI. This study elucidates the possible mechanisms from cumulative ecological risk to adolescent NSSI, and identifies positive stress beliefs as a protective factor, offering implications for prevention and intervention. Directions for future research are also discussed.</p>