<p>Despite the increasing incidence of non-suicidal self-injury (NSSI) among adolescents, available treatment methods are limited. This study aimed to evaluate the efficacy and durability of a newly developed family-integrated emotion regulation group therapy (ERGT). This study enrolled adolescents (aged 12–18 years) diagnosed with depression and recurrent episodes of NSSI (<i>n</i> = 73). They were randomly assigned to two groups: the trial group (<i>n</i> = 36) which received family-integrated ERGT; and the control group (<i>n</i> = 37) which received ERGT alone. Data on NSSI behavior, depressive symptoms, and impulsivity were collected using questionnaires, including the Adolescent Non-suicidal Self-injury Assessment Questionnaire (ANSSIQ), the Self-Rating Depression Scale (SDS), and Barratt’s Impulsivity Scale (BIS). All questionnaires were administered at five time points: baseline, immediately post-intervention, and at the 1-month, 3-month, and 6-month follow-ups. The values of heart rate variability (HRV) and event-related potential (ERP) were also collected before and after the intervention. Primary outcome: No significant between-group differences in the number of NSSI frequency were observed immediately post-intervention (<i>P</i> &gt; 0.05); however, the trial group showed significantly greater and progressively increasing reductions at all follow-ups (<i>P</i> &lt; 0.05). Secondary outcomes: Depressive symptoms and impulsivity showed a similar delayed but sustained improvement pattern. Post-intervention, the trial group also exhibited reduced N2, P3a, and P3b amplitudes and increased HRV, with no significant changes in the control group. Our findings suggest that family integration may enhance the long-term efficacy of ERGT in treating adolescent NSSI and associated emotional and cognitive dysregulation, supporting its clinical applicability.</p>