Objective To investigate changes in the betweenness in brain network and the functional connectivity between brain regions with abnormal betweenness among patients with refractory epilepsy based on graph theory.Methods Resting-state functional magnetic resonance imaging (RS-fMRI) was performed in patients with refractory epilepsy and healthy controls. The acquired RS-fMRI data were preprocessed with the Network Analysis module (Gretna) to calculate the betweenness value of each brain region. Statistical analysis was performed to detect the brain regions with differential betweenness values. The REST software was used to calculate the functional connectivity value between each pair of brain regions (regions of interest). Statistical analysis was performed to detect the differential functional connectivity.Results In the patients with refractory epilepsy, the betweenness value increased in the right triangular part of the inferior frontal gyrus and the right olfactory cortex and decreased in the right dorsolateral superior frontal gyrus, the left orbital part of the superior frontal gyrus, the left anterior cingulate gyrus, the right superior temporal gyrus, and the right inferior temporal gyrus, as compared with the healthy controls. The functional connectivity between the triangular part of the inferior frontal gyrus and the superior temporal gyrus was lower in the patients with refractory epilepsy than in the healthy controls.Conclusions There are changes in the betweenness in brain network and the functional connectivity between brain regions with abnormal betweenness among patients with refractory epilepsy, which affects the information communication between brain regions and may cause cognitive impairment in epilepsy patients.