The current study evaluated cultural values and family processes that may moderate associations between daily racial-ethnic discrimination and distress among Mexican-origin youth. Integrating micro-time (daily diary) and macro-time (longitudinal survey) research design features, we examined familism, family cohesion, and ethnic-racial socialization from youth-, mother-, and father- reports as potential buffers of daily associations between youth racial-ethnic discrimination and youth distress (negative affect and anger). The analytic sample, drawn from the Seguimos Avanzando study, included 317 Mexican-origin adolescents (Mage = 13.5 years) and their parents, recruited from the Midwestern United States. Results indicated that youth-reported familism and family cohesion significantly buffered daily associations between youth racial-ethnic discrimination and youth distress. In contrast, parent-reported familism and family cohesion and some aspects of ethnic-racial socialization exacerbated the discrimination to distress link. The implications of these results are discussed to inform efforts supporting the healthy development of Mexican-origin youth and their families.