Depressive symptoms in Latino youth have been related to both culturally-universal and culturally-based stressors. However, few studies have examined the unique contributions of culturally-based stressors above and beyond other types of stressors. Moreover, no past studies with Latinos have examined the role of culturally-based stressors within a hopelessness model of depressive symptoms, a cognitive model with the strongest empirical support in adolescence. The current study examined these issues in a sample of 171 Latino adolescents (7th-10th grades; mean age = 14; 46% male). The Latino adolescents were primarily Mexican-American (78%) and born in the United States (60%). Students completed measures during a school period on their experiences of parent-child conflict, economic stress, discrimination from peers, and acculturative stress as well as depressive symptoms and attributional style. The results indicated that culturally-based stressors (e.g., acculturative stress and discrimination) predicted greater depressive symptoms even when controlling for culturally-universal stressors (e.g., parent-child conflict, economic stress). Moreover, a negative attributional style moderated the relationship between culturally-universal stressors and depressive symptoms, but this was not the case for culturally-based stressors. Culturally-based stressors play an important role in depressive symptoms among Latino youth. These stressors predicted greater symptomatology even when controlling for other types of stressors and a negative attributional style. These findings suggest that there may be other cognitive risk factors associated with culturally-based stressors.