Many neuroimaging investigations focus on hepatic encephalopathy (HE); however, few investigate default-mode network (DMN) in the patients with HE and its underlying physiological relevance using resting-state fMRI. In this study, independent component analysis was used to retrieve components representing the DMN of patients with HE (n = 14) and healthy volunteers (n = 14). Four patients were excluded because of head motion (n = 3) and the artifact from the artificial tooth (n = 1). Comparison results between the two groups revealed significantly reduced functional connectivity in the right middle frontal gyrus and left posterior cingulate cortex in the HE patients. A statistical t-map from the comparison of venous blood ammonia levels and the z-scores of the DMN obtained from independent component analysis was computed in the HE group, which showed negative correlation with the changes in left angular gyrus. In conclusions, resting-state fMRI can be used to examine DMN changes in HE patients. Reduced functional connectivity in the right middle frontal gyrus and left posterior cingulate cortex consisting of the DMN and negative correlation between the functional connectivity changes in left AG and the venous blood ammonia levels support the notion of damages in functional organization of the central nervous system in HE patients. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc.