Objective：To study the expressions of human papillomavirus type 16/18-E6 (HPV16/18-E6 ), p53, and murine double minute-2 (MDM2) proteins in patients with laryngeal squamous cell carcinoma (LSCC) and their relationship with the development/progression of LSCC. Methods: The expressions of HPV16/18-E6, p53, and MDM2 proteins were detected by immunohistochemical method in 72 LSCC specimens, 24 specimens of precancerous larynx, 15 specimens of vocal cord polyp, and 8 normal laryngeal specimens, and their relations with clinicopathological factors of LSCC were statistically analyzed. Results: The positive rates of HPV16/18-E6 protein in the normal laryngeal, vocal cord polyp, precancerous larynx, and LSCC specimens were 0(0/8), 6.7%(l/15), 12.5%(3/24), and 37.5%(27/72); of p53 protein were 0(0/8), 13.3%(2/15), 25.0%(6/24), and 52.8%(38/72); and of MDM2 protein were 0(0/8), 6.7%(l/15), 37.5%(9/24), and 70.8%(51/72), respectively. The expressions of HPV16/18-E6, p53, and MDM2 were significantly different between the vocal cord polyp, the precacerous larynx, and the LSCC (P<0.05). The positive rates of HPV16/18-E6 and MDM2 protein in LSCC specimens increased significantly with the increase of histopathological grades (Ⅰ-Ⅲ) (P< 0.05). The positive rates of HPV16/18-E6 protein were positively correlated with the clinical staging and lymph nodes metastasis of LSCC (P<0.05). The expression of p53 was positively correlated with the expression of HPV16/18-E6 and MDM2 in LSCC patients (P<0.05). Conclusion: Inactivation of the p53 pathway and overexpression of HPV16/18-E6 and MDM2 may contribute to the genesis of human laryngeal cell carcinoma.