Background and aims: This study examines the relationship between social support (from parents and peers) and cigarette use, through the mediating effect of smartphone dependence, among adolescents. Study design: Prospective cohort study. Methods: A survey, conducted among 472 adolescents (average age = 16.2 years) attending classes in 3 schools in Lille, France, provides the data. The theoretical model features social support (parental and peer) and cigarette use, with smartphone dependence as a mediator, such that the authors simultaneously examine direct (support → cigarette use) and indirect (eg, peer support → smartphone dependence → cigarette use) paths. Results: The results illustrate that both parental support and peer support discourage cigarette use, but the indirect effect through smartphone dependence is positive. That is, smartphone dependence mediates the relationship between peer support and cigarette use. Parental support and peer support shape adolescents’ cigarette use and smartphone dependence differently, depending on the adolescents’ gender. Conclusions: Policy makers should acknowledge the positive effects of social support, the negative effect of smartphone dependence, and the importance of gender when developing anti-smoking policies and campaigns.