Non-suicidal self-injury (NSSI) is a clinically significant behavior with high relevance and prevalence, especially affecting approximately 17-18% of the adolescent population worldwide. The aim of this study is to perform a systematic review to evaluate the effectiveness of the available Specific Psychotherapeutic Interventions (SPI) focused on the reduction of NSSI behaviors. A systematic review was performed analyzing PsychINFO, MEDLINE, Web of Science, PubMed and Cochrane CentralRegister of Controlled Trials to identify studies of interest from January 2010 to December 2020. According to PRISMA guidelines, only 13 studies were included in the review. Six SPI were found to specifically and significantly reduce NSSI in adolescents: Developmental Group Psychotherapy (DGP), Therapeutic Assessment (TA), Cutting Down Program (CDP), Emotional Regulation Individual Therapy for Adolescents (ERITA), Treatment for Self-Injurious Behaviors (T-SIB) and Intensive Contextual Treatment (ICT). Furthermore, relevant improvements in anxiety and depression symptoms were observed. The results of this review demonstrate the effectiveness of these interventions, mainly the CPD and T-SIB, which are the only SPI that have been studied using Randomized Controlled Trial (RCT). Considering the clinical relevance and associated functional impairment of NSSI, more research is needed to replicate the results and to increase knowledge about SPIs.