Abstract: Objective: To investigate the expression and significance of p21 protein in the tissue of esophageal cancer and benign esophageal hyperplasia.Methods: Seventy-five cases of esophageal cancer specimen,15 benign esophageal hyperptasia specimen and 10 normal specimen were performed HE staining before immunohistochemistry analysis,and the expression of p21 protein was examined by immunohistochemical (S-P method).Results: The expression of p21 protein was negative in normal tissue,33.33% in benign esophageal hyperplasin tissue and 78.87% in esophageal cancer.The difference had statistical significance (P<0.01).The positive expression of p21 protein was 68.89% in high differential group,90.00% in medium differential group and 100.00% in low differential group.The difference was statistically significant (P<0.05).Conclusions: The expression of p21 protein may demonstrate the differential degree of esophageal cancer,guide the clinical therapy and help to judge the prognosis.P21 protein is regarded as a reliable label in early diagnosis of esophageal cancer.