BackgroundNon-suicidal self-injury (NSSI) among medical students represents a critical public health concern, yet the protective mechanisms and their effectiveness across different demographic contexts remain poorly understood. This study investigates how social support mediates the relationship between negative life events and NSSI, while examining the moderating effect of urban-rural origins.MethodsA cluster sampling approach was employed to survey 1,130 first-year medical students (471 males, 659 females; mean age 18.15 ± 0.63 years; response rate: 98.5%) at Xiamen Medical College, including 473 urban and 657 rural students. Participants completed the Adolescent Self-Rating Life Events Checklist, Social Support Rating Scale, and Adolescent Self-Injury Questionnaire. Harman’s single-factor test confirmed no significant common method bias. Hayes’ PROCESS macro (Model 7) was used to test the moderated mediation model, with bootstrapping (5,000 resamples) for significance testing.ResultsCorrelation analysis revealed significant associations between life events and NSSI (r = 0.28, p