Abstract: Objective To study the expression of human papillomavirus 16／18E6（HPV16／18E6）， p53 and EZH2 protein in laryngeal squamous cell carcinoma（LSCC）， and discuss the correlation among them. Methods The expression of HPV16／18E6， p53 and EZH2 proteins were detected with En Vision immunohistochemical method in 113 cases of paraffinembedded tissues including 78 LSCC specimens， 15 specimens of normal tissue adjacent to cancer and 20 specimens of vocal cord polyp. Their correlations with clinicopathological factors and the interrelation of the expression of HPV16／18E6， p53 and EZH2 proteins in laryngeal cancer were analyzed. Results The positive expression rates of HPV16／18E6， p53 and EZH2 protein in the LSCC group were 47.4％（37／78）， 60.3%（47/78） and 65.4％（51／78）respectively， which were significantly higher than those in the other groups. The increasing expression of HPV16／18E6 and EZH2 in LSCC was associated with T stage， while p53 and HPV16／18 expression was positively related to lymph node metastases. Additionally， the positive rates of p53 protein in LSCC increased significantly with the increase of histopathological grades. The positive expression of p53 and EZH2 was consistent（kappa=0.451, P＜0.05）. Conclusion Overexpression of HPV16／18E6， p53 and EZH2 proteins in LSCC contributes to the genesis and development of tumor. Increased expression of EZH2 protein in LSCC may be partly induced by p53 protein inactivation which promote tumor growth and progression.