The objectives of the present study are the following ones: 1) to study the use of drugs, the prosocial behaviour and the problem-solving skills with respect to age and gender, and 2) to analyze the association of both the prosocial behaviour and the problem-solving skills with the use of drugs. An descriptive cross-sectional study was performed, amongst a sample of 567 students in Spanish Compulsory Secondary Education (48.14% males) with an age range from 14 to 17 years (M = 14.92; SD = .90). Statistically significant differences were found concerning alcohol use and the prosocial behaviour with respect to gender, as well as concerning alcohol and cannabis use with respect to age. When we controlled the effect of age and sex in the regression models, the variable that best predicted alcohol and cannabis use was prosocial behavior. The results from this study enhance the importance of tailored interventions based on the promotion of prosocial behaviours as fundamental protective factor for substances use such as alcohol and cannabis amongst adolescents.