Background: There is an established link between depression and drug use among adolescents. This relationship holds true for Hispanic youth, for whom familial relationships are especially impactful toward health outcomes. Purpose: Our purpose was to examine the relationships between family functioning and adolescent and parent depressive symptoms, and the indirect effects of depressive symptoms on the relationship between family functioning and adolescent drug use. Methods: Participants were 231 Hispanic adolescents (52.9% female, M[subscript age] = 13.90 ± 1.37) and their parents (93.0% female, M[subscript age] = 43.24 ± 6.64) enrolled in an RCT. Data on depressive symptoms, drug use, and family functioning were collected and a latent variable was specified using four indicators of family functioning (positive parenting, monitoring, communication, and involvement). A structural equation model approach was utilized. Results: Youth family functioning predicted youths' depressive symptoms which predicted their own drug use. Youths' depressive symptoms mediated the relationship between youth family functioning and drug use. Discussion: Findings suggest that adolescents' perceptions of family functioning plays a role in preventing depressive symptoms and drug use among Hispanic youth. Translation to Health Education Practice: Teaching students of the role that family support and depressive symptoms play in the manifestation of drug use may be an effective approach to preventing drug use.