Gp96 (GRP94) is a chaperone that is responsible for molecular folding and assembly of proteins. To investigate correlations among Gp96 expression, sensitivity to radiotherapy and clinical features of nasopharyngeal carcinoma (NPC), the expression of Gp96 in 98 NPC samples was analyzed by immunohistochemistry and Western blotting at the protein level, and by real-time PCR at the mRNA level. Clinicopathological features, including stage, sex, grade and survival, were compared between the high and low Gp96 expression groups. As a result, Gp96 was expressed at a higher level in NPC tissues than in noncancerous nasopharyngeal mucosa (p = 0.001). Univariate analysis suggested that a higher Gp96 expression level was associated with significantly decreased disease-free and 5-year survival rates (p = 0.000, p = 0.000, respectively). Multivariate Cox proportional-hazard regression analysis, which adjusts for clinicopathological variables, indicated that it was only associated with the 5-year overall survival rate (p = 0.002). Furthermore, patients with high Gp96 expression levels were significantly more resistant to radiotherapy (p = 0.001). These data are the first indication of a positive correlation between Gp96 expression levels and radiosensitivity and 5-year survival rate. Gp96 might serve as a novel candidate marker for predicting the long-term prognostic outcome of NPC. Copyright (c) 2012 S. Karger AG, Basel