<p>Non-suicidal self-injury (NSSI) has become a significant public health issue, garnering attention from across society. While it has been established that family economic hardship serves as a risk factor for adolescent NSSI, the underlying mechanisms connecting these two factors remain to be fully elucidated. Based on a gene-environment interaction perspective, this research explored whether peer victimization acts as a mediator in the link between family economic hardship and adolescent NSSI, and whether the COMT rs4680 polymorphism moderates this indirect path. A total of 477 Chinese adolescents (<i>M</i>_<i>age</i>=12.81 years, <i>SD</i> = 0.48 years, 47.80% girls) participated in two surveys conducted six months apart. After controlling for age, gender, and NSSI at Time 1, peer victimization significantly mediated the relationship between family economic hardship and adolescent NSSI. Furthermore, the impact of family economic hardship on peer victimization was only significant in adolescents with the A allele of the COMT rs4680 polymorphism. Additionally, the positive association between peer victimization and NSSI was much stronger for adolescents with the A allele than for those with the GG genotype. These findings shed light on the risk factors for NSSI in adolescents experiencing family economic hardship. They provide a strong theoretical basis and practical insights for targeted interventions aiming to prevent adolescent NSSI.</p>