BACKGROUND: The presence of emotional problems may trigger drug abuse. AIM: To determine the association between illicit drug use and severity of depression symptoms among students of public secondary schools in Santiago, Chile. MATERIAL AND METHODS: A probabilistic sample of 2,597 adolescents aged between 12 and 18 years (45% women), attending first year in public high-schools in Santiago, answered self-report questionnaires about consumption, during the last 30 days ,of alcohol, tobacco and marihuana, and the Beck Depression Inventory - II. Logistic regression models were used to study the association between drug use and severity of depression symptoms, adjusting by sex. RESULTS: Tobacco and marihuana use was reported by 38 and 13% of students, respectively. Frequency of consumption was significantly higher among women. Mild, moderate or severe depressive symptoms were found among 16%, 14% and 9% of students, respectively. Depressive symptoms were more common among women. There was a significant association between drug use and severity of depression among participants of both genders. CONCLUSIONS: The association between depressive symptoms and drug use should be considered on the design of treatment guidelines for these health problems in Chile.