Parents' familism values predict a variety of Latinx American youth's academic adjustment. However, it is unclear how cultural values such as familism interact with youth's brain development, which is sensitive to sociocultural input, to shape their academic adjustment. Using a sample of 1916 Latinx American American youth (mean age = 9.90 years, SD = .63 years; 50% girls) and their primary caregivers (mean age = 38.43 years, SD = 6.81 years; 90% mothers) from the Adolescent Brain Cognitive Development Study, this study examined the longitudinal relation between parents' familism values and youth's school disengagement, as well as the moderating role of youth's neural sensitivity to personal reward. Parents' familism values predicted youth's decreased school disengagement 1 year later, adjusting for their baseline school disengagement and demographic covariates. Notably, this association was more salient among youth who showed lower (vs. higher) neural activation in the ventral striatum and the lateral OFC during the anticipation of a personal reward. These findings underscore the protective role of familism for Latinx American youth, highlighting the necessity of developing culturally informed interventions that take into consideration of youth's brain development.