Abstract: ObjectiveTo evaluate the association between Tap2379/Tap2665 genetic polymorphisms/ HLA-DR9 immune-associated gene and esophageal cancer (EC) in a high incidence Kazakh of Xinjiang. MethodsA case-control study was conducted with 194 cases of EC and 388 controls. Tap2379/Tap2665 genotypes were detected by PCR-RFLP and HLA-DR9 allele gene were identified by PCR.The conditional logistic regression model was performed in this study. ResultsTap2379 genotype frequencies of esophageal cancer group was different from the controls(χ²=18.247，P<0.05，OR=2.347，95%CI：1.587~3.471)；Tap2665 genotype did not find this difference(χ²=2.175，P>0.05，OR=1.317，95%CI：0.919~1.899); HLA-DR9 allele positive of case group was different from the controls(χ²=13.443,P<0.05,OR=2.343,95%CI：1.486~3.693).Multivariate conditional logistic regression analysis showed: Tap2379 genetic polymorphisms/ HLA-DR9 gene and history of esophageal or stomach disease were risk factors of Kazakh esophageal cancer. The interaction analysis showed Tap2379 genetic polymorphisms with HLA-DR9 allele gene significantly increased risk to the development of esophageal cancer 5.302(95%CI：2.363~11.900). Conclusion Tap2379 genetic polymorphisms and HLA-DR9 allele gene are important risk for EC, Tap2665 genotype did not found this action. Tap2379 and HLA-DR9 showed an additive risk to develop esophageal carcinoma.