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Purpose: This study aimed to identify the prevalence of alcohol and cigarette use and assess its relationship with socio-environmental, psychological, violent and behavioral factors among a sample of high school students from Lima and Callao, Peru. Methods: We utilized the data from a cross-sectional study conducted by the Yonsei Global Health Center in collaboration with the Korea International Cooperation Agency (KOICA) Peru office in November 2016. The total sample size of this study was 1,477 students. For analysis, we used bivariate and multivariate logistic regression to calculate the unadjusted and adjusted odds ratios and their respective 95% confidence intervals. Results: The current prevalence of alcohol and cigarette use among adolescents was found to be 24.2% and 12.1%, respectively. Alcohol use was affected by age, friends' alcohol use, experience of physical fighting, and involvement in other risk behaviors (smoking, drug use, and sexual intercourse). Cigarette use was affected by perceived academic performance, friends' cigarette use, and involvement in other risk behaviors (drinking, drug use, and sexual intercourse). Furthermore, students who received affection from their parents and whose parents monitored their activities were less likely to report using both alcohol and cigarettes. Conclusion: Alcohol and cigarette use among Lima and Callao adolescents is affected by socio-environmental, violent and behavioral factors. Alcohol and cigarette use prevention initiatives should promote positive parenting practices, family togetherness, and a supportive school climate. In addition, it is needed to establish peer-led programs that promote behavioral changes in students and strengthen social relations without the presence of alcohol, cigarettes, and other harmful substances.