This study investigated the trajectories of interpersonal stress and psychological pain and their effects on self-harm behaviors in adolescents and explored the reciprocal associations between interpersonal stress and NSSI/SA. The participants included 1149 adolescents (50.3% women; Mage = 12.86, SD = 0.69) who participated in three waves of data collection. Latent class growth models and cross-lagged panel models were used to identify subgroups of individuals and interactions between interpersonal stress and NSSI/SA. Controlling for sex and age, compared to the low interpersonal stress class, the moderate to high and increasing classes have higher risks of NSSI and SA. Compared to adolescents in the low increasing feelings with high increasing avoidance class, those in the low increasing feelings with low decreasing avoidance class reported lower probabilities of NSSI and SA. Pain avoidance and painful feelings mediated the pathway from interpersonal stress to NSSI/SA, whereas pain arousal mediated the pathway from NSSI/SA to interpersonal stress. Shared impact of interpersonal stress and distinct effects of psychological pain over time on maintaining and distinguishing self-harm behaviors were found. Adolescent crisis interventions should simultaneously focus on building social networks within the school context and regulating maladaptive minds.