We evaluated the clinical significance of p16 and Ki-67 expressions in esophageal squamous cell carcinomas. Operative specimens obtained from 64 patients with esophageal squamous cell carcinomas were investigated by staining with antibodies against p16 and Ki-67. The possible correlations among p16 and Ki-67 expression, clinicopathologic factors and prognosis were studied. The expression of p16 was observed in 68.9%, and it related to histologic classification, lymphatic invasion and clinicopathological stage. Survival rate was significantly better in the patients with p16 positive tumors than in those with p16 negative tumors. Ki-67 positive index (Ki-67-PI) related to only histologic classification. It is suggested that immunohistochemical assessment on the p16 expressions would be useful to select more suitable treatment of squamous cell carcinoma of the esophagus.