Background and Objectives: Adolescents as a high-risk group are prone to addiction. This research aimed to investigate the role of depression, family relationships, and self-efficacy in the prediction of susceptibility to addiction among adolescents.Methods: The present research was a descriptive-correlational study carried out on 546 adolescents of Lorestan province’s high school in school year 2014-2015. The samples were selected through multiple cluster sampling method. Participants responded to demographic characteristics, addiction potential, depression, family relationships, and self-efficacy questionnaires. Data were analyzed using Pearson’s correlation coefficient and stepwise multiple linear regression.Results: In this study, depression, family relationships, and self-efficacy was significantly correlated with addiction potential (p<0.01). Multiple regression analysis indicated that depression, family relationships, and self-efficacy significantly predicted 37.2%, 2%, and 2.1% of addiction potential variance, respectively (p<0.0001).Conclusion: The results of this study indicated that depression, family relationships, and self-efficacy are important in the prediction of addiction potential, so that these factors can explain the high degree of variability of addiction potential among adolescents.