Psychological resilience refers to the ability to bounce back from adversity and previous studies have shown sex differences in psychological resilience. Here, we employed amplitude of low-frequency fluctuations (ALFF) to investigate sex differences in the relationship between resting-state brain activity and psychological resilience in 231 healthy adolescents. Behaviorally, we found that males were more resilient than females. Neurally, a positive correlation between psychological resilience and the ALFF in the right orbitofrontal cortex was detected among males while a negative correlation was observed among females. Together, our study provided the first evidence of sex-specific neurofunctional substrates underlining psychological resilience in adolescents.