Abstract: Objective To evaluate the association between HLA-DR9 genetic polymorphisms and esophageal cancer (EC) in a Kazakh population of high incidence area at Xinjiang,China.Methods A case-control study was conducted with 170 EC cases and 340 controls.HLA-DR9 was identied by PCR-SSP.Logistic regression model was performed to identify fisk factors.The strata method was adopted in interaction analysis.Results The frequency of HLA-DR9 gene in the cases and controls were 22.9% and 9.1%,respectively,with significant difference (χ²=18.29,P=0.000,OR=2.97).The genotype frequncy of esophageal cancer was different from that of the controls (χ²=18.29,P=0.000;OR=2.97,95% Cl:1.78-4.96).The proportion of history of esophageal or stomach disease in esophageal cancer group was 26.5%,while the proportion was 12.9% in the controls (OR:2.42,95% Cl:1.52-3.86).Family history of esophageal cancer was 18.20% in cases,while the proportion was 8.80% in the controls (OR:2.31,95% Cl:1.34-3.96).Multivariate Logistic regression analysis showed that HLA-DR9 genotype,history of esophageal or stomach disease and family history of esophageal cancer were risk factors of esophageal cancer.Gene-environment interaction analysis showed there was an interaction of HLA-DR9 genotype with history of esophageal or stomach disease and family history of esophageal cancer.Conclusion The HLA-DR9 genotype,history of esophageal or stomach disease and family history of esophageal cancer are important risk for EC,and there is a synergistic interation between HLA-DR9 gene and the history of esophageal or stomach disease and family history of esophageal cancer.HLA-DR9 gene can be used as biomarker for prevention of EC in Kazakh population.