Abstract: Objective To study the relationship between the p16 protein expression and biological behavior of esophageal squamous cell carcinoma in Kazak. Methods Use immunohistochemistry (SP method)to detect 30 cases of esophageal squamous cell carcinoma and 60 cases of p16 protein in normal esophageal mucosa. Results The expression of p16 protein was found positive in 56 cases among 60 cases of normal esophageal mucosa (positive rate 88.33%).The p16 protein positive rate of 30 patients with esophageal squamous cell carcinoma was 46.67% (14/30).With the increasing degree of malignancy and disease progression，the positive rate decreased gradually.The positive rate of p16(75%) in well-differentiated squamous cell carcinoma was significantly higher than that of poorly differentiated squamous cell carcinoma (25%)(P<0.05). Conclusion p16 protein expression loss may be related to the occurrence of esophageal squamous cell carcinoma in Kazak.