A sample of 189 Mexican-heritage seventh grade adolescents reported their substance use, while one of the child’s parents reported parent’s acculturation and communication, involvement, and positive parenting with his or her child. Higher levels of parental acculturation predicted greater marijuana use, whereas parent communication predicted lower cigarette and marijuana use among girls. A significant parent acculturation by parent communication interaction for cigarette use was due to parent communication being highly negatively associated with marijuana use for high acculturated parents, with attenuated effects for low acculturated parents. A significant child gender by parent acculturation by parent positive parenting interaction was found. For girls, positive parenting had a stronger association with lower cigarette use for high acculturated parents. For boys, positive parenting had a stronger association with reduced cigarette use for low acculturated parents. Discussion focuses on how acculturation and gender impact family processes among Mexican-heritage adolescents.