As a personality trait, hope refers to the motivational tendency for initiating actions and generating routes to achieving goals and plays a protective role in anxiety. Here, we investigated the neural basis of hope in 231 adolescents using resting-state functional magnetic resonance imaging (RS-fMRI). We found that trait hope was negatively associated with the spontaneous activity in the bilateral medial orbitofrontal cortex (mOFC). Further mediation analyses revealed that trait hope mediated the relationship between the mOFC activity and trait anxiety. Taken Together, our findings might provide the initial evidence for the brain-personality mechanisms protecting against anxiety.