Background: With the increasing number of multicultural adolescents, concerns about their healthy development are also on the rise. This study aimed to examine the influence of mothers’ acculturative stress on adolescents’ depression in multicultural families with respect to the moderating effect of sex.Methods: A series of regression analyses were conducted using a sample of 1,052 adolescents from multicultural families composed of a foreign-born mother and a Korean father based on the 9th wave of the Multicultural Adolescents Panel Study (MAPS).Results: First, foreign-born mothers’ acculturative stress positively and significantly influenced adolescents’ depression. When the level of acculturative stress increased, so did the level of depression. Second, the influence of mothers’ acculturative stress on adolescents’ depression was moderated by sex. The influence was larger for female than for male adolescents.Conclusions: Based on its findings, this study discussed intervention strategies to address depression among multicultural adolescents.