We aimed to investigate alterations in regional and network-level neural function in patients with hepatitis C virus (HCV) infection and examine the association between these alterations and patients’ cognition dysfunction. HCV-infected patients performed significantly worse in the cognitive tests. In the HCV group, amplitude of low-frequency fluctuation (ALFF) decreased in two prefrontal regions (Region-1and Region-2). The HCV group showed lower FC between the Region-1 and right middle frontal gyrus; whereas they presented an increase in FC between Region-2 and bilateral parietal-temporal cortex. HCV infection affects brain function, including local intrinsic neural activity and global functional integration.