As a stressful environment in families, mothers’ depressive symptoms might increase children’s risks of developing behavioral problems by exacerbating genetic influences. Using data from the nationally representative Early Childhood Longitudinal Study-Birth Cohort data of approximately 750 pairs of twins, we examined whether genetic influences on preschoolers’ behavioral problems depended upon mothers’ depressive symptoms. Results indicated that the genetic etiology for both internalizing and externalizing behaviors varied with maternal depressive symptoms at 9-months child age. Genetic effects on externalizing behaviors increased as mothers’ depressive symptoms increased; however, genetics effects on internalizing behaviors increased when depressive symptoms either increased or decreased from the median level. These different patterns of interactive effects suggest potentially different mechanisms for the etiology of children’s externalizing and internalizing behaviors.