Neuroinflammatory processes are directly involved in the pathogenesis of non-suicidal self-injury (NSSI) among adolescents. However, their role in predicting the outcome of adolescent NSSI is unknown. This study aimed to explore the relationship between inflammatory cytokines and their effect on NSSI treatment through a prospective investigation.Thirty-two healthy adolescents and 199 adolescents who had engaged in NSSI were recruited. Blood samples were obtained from all participants to determine the concentration of inflammatory cytokines at enrollment. Thereafter, the NSSI group completed surveys on their NSSI behaviors after 3, 6, and 12 months. The outcomes of their NSSI behaviors were evaluated using the indexes of NSSI number and NSSI impulsivity.The results showed that the mean NSSI number and NSSI impulsivity of the participants both showed a decline tendency over time. However, regarding the NSSI number, the significant treatment effect only emerged after 6 months. The abnormal rates of IL-1βand IL-8 levels of the NSSI group were significantly higher than those of healthy controls (χ2 = 3.945, 27.394; P < 0.05). In the regression models, high IL-8 level (β: 0.225, 95% CI: 0.001, 0.005; p = 0.001), high TNF-α level (β: 0.157, 95% CI: 0.023, 0.244; p = 0.018), and low IL-10 level (β: - 0.261, 95% CI: - 2.678, - 0.901; p = 0.017) could predict the treatment effect of NSSI number. High level of IL-8 (β: 0.233, 95% CI: 0.002, 0.009; p = 0.001) and long duration of medical treatment (β: 0.285, 95% CI: 0.234, 0.649; p < 0.001) could predict the treatment effect of NSSI impulsivity. When considering the two indexes together, the role of screened-out cytokines, IL-8 (OR = 1.065, 95% CI: 1.032,1.099; p < 0.001), TNF-α (OR = 1.839, 95% CI: 1.063, 3.182; p = 0.029) and IL-10 (OR = 0.031, 95% CI: 0.002, 0.541; p = 0.017), were still stable.Employing the assessment of inflammatory cytokines among adolescents who engage in NSSI may be helpful in predicting their treatment outcome and designing other suitable treatment schemes in advance.registered in https://www.medicalresearch.org.cn/ . Retrospectively registered: registered in https://www.chictr.org.cn/ .ChiCTR2500097375. Date of registration: 18th February, 2025.© 2025. The Author(s).