Abstract: The present study aimed to examine whether emotion regulation strategies mediated the relationship between negative life events and adolescents’ mobile phone addiction, and whether the direct and indirect effects in the mediation model were moderated by self-control. A sample of 461 adolescents was invited to complete a battery of self-report questionnaires. The results indicated that: (1) negative life events not only directly predicted adolescents’ mobile phone addiction but also exerted an indirect effect through negative emotion regulation strategies; that is, negative emotion regulation strategies played a partial mediating role in the relationship between negative life events and adolescents’ mobile phone addiction. Whereas the mediating role of positive emotion regulation strategies was not significant. (2) self-control moderated both the effect of negative life events on adolescents’ negative emotion regulation strategies and the effect of adolescents’ negative emotion regulation strategies on their mobile phone addiction. The moderated mediation model hypothesis was thus supported, and this result also highlights the role of high self-control in protecting at-risk adolescents from addictive behaviors. These results suggest that parents and teachers should pay attention to adolescents experiencing negative life events, provide support for them, and meanwhile, offer adaptive emotional regulation strategies and self-control training to prevent adolescents’ mobile phone addiction.