Objective:To investigate the enhancer of zeste homolog 2(EZH2) expression in tongue squamous cell carcinoma (TSCC) and its relationship with various clinicopathological parameters. Methods:The EZH2 protein expression in 52 cases of TSCC and 12 cases normal tongue samples was examined by immunohistochemistry. Based on these patients’ information and their follow-up data,the correlations of the EZH2 level with patients’ clinicopathological characteristics and overall survival were further evaluated by statistical analyses using Fisher exact test and Kaplan-Meier method respectively. Results:The EZH2 was over-expressed in TSCC,which was statistically different from that in normal tongue(P < 0.001). EZH2 over-expression was found to be associated with tumor grades(P = 0.033),cervical lymph node metastasis(P = 0.036) and the presence of local invasion (P = 0.012),but not with gender,age,tumor size and clinical stage (P > 0.05). The overall survival rates in patients with EZH2 high expression were significantly lower than those in patients with EZH2 low expression as estimated by Kaplan-Meier method and Log-rank test (P = 0.028). Conclusion:EZH2 is over-expressed in TSCC and its upregulation is associated with tumor grades,cervical lymph node metastasis,local invasiveness and poor prognosis.