A significant proportion of patients with nasopharyngeal carcinoma (NPC) will develop regional relapse or distant metastasis after treatment. So, to find valuable prognostic factors becomes very important. To elucidate the expression of ezrin in NPC and its correlation with patients' clinicopathologic characteristics, time to progression, and overall survival, immunohistochemistry stains for ezrin were applied to 200 tissue specimens of NPC. Ezrin expression had no significant correlation with sex, age, primary tumor stage (T), Epstein-Barr virus (EBV) VCA-IgA antibody, EBV EA-IgA antibody, and EBV DNA copy except primary nodal status (N; p = .032). Increased ezrin expression was significantly related to higher lymph nodal metastatic rate (p < .004). Among ezrin (negative/weak), ezrin (moderate), and ezrin (intense) groups, there was a significant difference for median time to progression (not reached vs. 63.2 months vs. 46 months, P < .001) and median overall survival (100.7 months vs. 80.8 months vs. 70.6 months, P < .001). Ezrin expression status was an independent prognostic factor in multivariate (Cox) analysis. Ezrin, which was significantly correlated to prognosis of disease, may be involved in the tumorigenesis, progression, and invasion of NPC. Thus, our data offer the possibility of future therapeutic targets.