Adenocarcinoma of esophagus (AE) is a complex disease, affected by a variety of genetic and environmentalfactors. Much evidence has shown that the MutY glycosylase homologue (MUTYH) plays a key role in thepathogenesis of many cancers. However, there have been no reports on influence on AE in the Han Chinesepopulation. The objective of this study was to investigate this issue. A gene-based association study was conductedusing three single nucleotide polymorphisms(SNPs) reported in previous studies. The three SNPs (rs3219463,rs3219472, rs3219489) were genotyped in 207 unrelated AE patients and 249 healthy controls in a case-controlstudy using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Theresults revealed that the genotype distribution of rs3219472 differed between the case and control groups(OR=1.66,95%CI=1.11-2.48, P=0.012 ), indicating that an association may exist between MUTYH and AE. Thesefindings support a signifcant role for MUTYH in AE pathogenesis in the Han Chinese population.