Background: Non-suicidal self-injury (NSSI) has become one of the serious public health concerns among adolescents. Factors like family and social environment of adolescents may be important determinants of the NSSI. This study aimed to investigate the relationship between family psychological function and perceived social support with the NSSI experience among adolescents. Study design: A cross-sectional study. Methods: Overall, 4216 high school students (15-18 yr old) of Tabriz City, northwestern Iran were selected using multi-stage cluster random sampling method in October and November 2017. Participants completed survey including demographic characteristics, NSSI status, Iranian family psychological function, and perceived social support. After six months, NSSI status was reassessed. The data were analyzed using logistic regression model. Results: 8.5% of the students had NSSI experience. In addition, the weak family psychological function increased the odds of experiencing the NSSI by 13 times compared to the strong psychological function (OR = 13.15, 95% CI: 7.19, 23.80). Besides, the low level of perceived social support increased the odds of experiencing the NSSI by about 7 times compared to the high perception of social support (OR= 6.67, 95% CI: 4.01, 11.11). Conclusion: Low levels of psychological functioning of the families and perception of social support significantly can increase the odds of experiencing the NSSI among adolescents. Therefore, special attention should be paid to these factors in the development of relevant preventive programs in adolescence period.