This study examined gender differences in how internalizing and externalizing symptoms affect adolescents’ decisions about smoking in Chile, where girls smoke at some of the highest rates in the world. In multivariate logistic regression analyses with 607 adolescents, internalizing symptoms, such as depressed mood and anxiety, predicted smoking among girls more than boys, with girls who were low in internalizing symptoms being more likely to smoke than those who were high in internalizing symptoms. In Chile’s high-risk context, internalizing symptoms may be indirectly protective for girls by decreasing their exposure to peer pressure and related influences that encourage cigarette use.