Objective To assess radiation-induced changes of brain gray matter volume (GMV) in nasopharyngeal carcinoma (NPC) patients before and after radiation therapy (RT) using voxel-based morphometry (VBM) and investigate possible correlation with overall cognitive scores. Methods A total of twenty four patients with pathologically diagnosed as NPC and treated with the first RT were recruited for the study. High resolution three-dimensional T1 weighted image acquisition was conducted respectively in each patient before radiotherapy (pre-RT) and within 6 months after completion of radiotherapy (post-RT). Data were processed using the SPM8 based VBM8 toolbox. Over the same period, the Montreal Cognitive Assessment (MoCA) scale was used to assess the overall cognitive function of all patients. Results We detected significantly decreased GMV in the left cerebellum, right medial frontal gyrus and left precentral gyrus within 6 months after RT compared to pre-RT (P＜0.05, FDR corrected, cluster size＞ 50 voxels). Moreover, GMV loss in the right medial frontal gyrus was positively correlated with MoCA scores. Conclusion VBM approach may sensitively detect the abnormal GMV in the NPC patients after RT, which might provide new insight into the pathogenesis of radiation-induced cognitive impairment.