Negative risk-taking behaviors refer to voluntary behaviors that lead to more harm than good. Low self-control is a crucial predictor of adolescents’ negative risk-taking behavior, but its internal mechanisms require further exploration. To reveal the working process underlying the association between self-control and adolescents’ negative risk-taking behaviors, we investigated the mediation of regulatory focus and the moderation of sense of power. A total of 2018 students (37.6% males) from two universities in Guangzhou, China, participated in a survey that investigated their self-control, negative risk-taking behavior, regulatory focus and sense of power. The results revealed that after controlling for the adolescents’ sex and their parents’ educational level, prevention focus partially mediated the association between self-control and negative risk-taking behavior. Moreover, sense of power moderated the association between self-control and prevention focus. Furthermore, the association between self-control and negative risk-taking behavior through prevention focus was stronger among adolescents with a high sense of power than among those with a low sense of power. Therefore, our findings suggest that regulatory focus and sense of power might be the mechanisms that explain how self-control is related to negative risk-taking behavior. These results thus provide a foundation for the prevention of and intervention in adolescents’ negative risk-taking behavior.