Objective To investigate the inter-hemispheric resting-state functional connectivity and its relation with cognitive function in patients with end-stage renal disease (ESRD) by using resting-state functional magnetic resonance imaging (rs-fMRI) based on voxel-mirrored homotopic connectivity (VMHC). Methods A total of 52 patients with ESRD (ESRD group), admitted to our hospital from July 2018 to January 2019, were enrolled; 36 age-, gender-, and education level-matched healthy controls (HCs group) were collected at the same time period. The cognitive function of all subjects was assessed by Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT)-A, TMT-B and Symbol Digit Modalities Test (SDMT). The rs-fMRI and 3D-T1WI data were acquired from all subjects; after image preprocessing, VMHC values between brain hemispheres were calculated and the regions with significantly different VMHC values were obtained. The correlations between VMHC values in significant regions and cognitive scale scores were analyzed. Results MMSE, MoCA and SDMT scores of ESRD patients were significantly lower than those of the HCs group (P<0.05), and ESRD patients took longer time to complete TMT-A and TMT-B tests than the HCs group (P<0.05). As compared with that of the HCs group, significant decrease of VMHC values of ESRD patients was found in the hippocampus, lingual gyrus, superior temporal gyrus, caudate nucleus and anterior cingulate gyrus (P<0.01, AlphaSim correction); the VMHC values of the anterior cingulate gyrus and hippocampus were positively correlated with MMSE and MoCA scores (P<0. 05). Conclusion Significant abnormal inter-hemisphere functional connectivity is found in patients with ESRD, which is associated with cognitive function.