Non-suicidal self-injury (NSSI) in adolescence is a serious public health problem. Although self-compassion is a protective factor of mental health difficulties in adult populations, its potential impact on adolescence remains scarcely explored. Therefore, we aimed to test whether self-compassion can mitigate the impact of daily peer hassles and depressive symptoms on NSSI. The participants were 643 adolescents (51.6% female) with ages between 12 and 18 years, from middle and secondary schools. Self-report questionnaires were used to measure daily peer hassles, depressive symptoms, self-compassion and NSSI. Daily peer hassles were positively correlated with depressive symptoms and NSSI. Self-compassion was inversely associated with daily peer hassles and depressive symptoms and NSSI. Path analysis showed that self-compassion had a moderator effect on the association between depressive symptoms and NSSI. Results suggest that self-compassion can be a protective process, as it may buffer against the impact of depressive symptoms on NSSI. This study presents preventive and clinical implications for educators and therapists working with adolescents.