Background: Previous literature has shown a negative relationship between parental stress and youth moderate to vigorous physical activity (MVPA). This study examined (1) the relationship between parental stress and adolescent MVPA, (2) the moderating role of family communication on this relationship, and (3) gender differences in these effects among overweight and obese Hispanic adolescents. Methods: Hispanic adolescents (N = 280, 52% female, 13.0 [0.8] y old, 44% obese, 12% severely obese) and their parents (88% female, 44.9 [6.5] y old) completed baseline measures for an efficacy trial. Adolescents self-reported MVPA in minutes per week for work, transportation, and recreation using a validated measure. Multiple regression analyses with interaction terms and multigroup methods were conducted. Results: There was a negative effect of parental stress on adolescent MVPA (β = −0.15, t = −2.018, P ≤ .05). This effect was moderated by family communication (β = 0.20, t = 2.471, P = .01), such that the association between parental stress and youth MVPA was stronger for adolescents with low levels of family communication. Furthermore, a multiple group model showed that the interaction was significant for boys (β = 0.27, t = 2.185, P = .03), but not for girls. Conclusions: Findings provide support that addressing parental stress and family communication may help facilitate MVPA among Hispanic boys, the most at-risk group for pediatric obesity.