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The aim of this study was to explore the association of the genetic polymorphism of EPHX1 and EPHX2 with the susceptibility to chronic benzene poisoning(CBP).A case-control study of 268 patients with CBP and 268 healthy workers matehed by age and sex,all of whom were occupationally exposed to benzene,was conducted.The single nucleotide polymorphisms(SNPs,rs2854451,rs3738047,rs2234922 and rs1051741)of EPHX1 gene and the SNP (rs751141)of EPHX2 gene were tested by the TaqMan PCR method.In the subjects carrying the genotype of EPHX1 rs3738047 GG,the risk of CBP was decreased in the individuals simultaneously carrying EPHX1 rs2234922 G (P=0.02).Alteatively,in the subjects carrying the genotype of EPHX1 rs2234922 AA,the risk of CBP was increased in the individuals simultaneously carrying the allele of EPHX2 rs751141A (P=0.03).It was also found that there were potential interactions between alcohol consumption and the polyorphism of EPHX1 rs1051741(XH2=5.28,P=0.02)or rs2234922(XH2=6.71,P=0.01).Compared to individuals with EPHX1 rs1051741 CC or rs2234922AA genotype in the drinkers,the risk of CBP in those carrying genotypes of EPHX1 rs1051741 CT+TT or rs2234922 AG+GG was decreased,respectively(P=0.04,P＜0.0 1).Haplotype analysis of polymorphisms in EPHX1 showed that the risk of CBP was increased in the subjects with haplotype 2 (rs2854451-A,rs3738047-G,rs2234922-A,rs1051741-C)or haplotype 4(rs2854451-G,rs3738047-A,rs2234922-G,rs1051741-T),but decreased in those with haplotype 6 (rs2854451-G,rs3738047-G,rs2234922-G,rs1051741-T)or haplotype 10(rs2854451-A,rs3738047-A,rs2234922-G,rs1051741-T),respectively.Logistic regression analysis revealed that smoking might play a role in modifying the risk of CBP (OR=0.313,95%CI:0.123-0.794,P=0.015).The genetic polymorphism in EPHX1 may be associated with the risk of CBP in the Chinese occupational population and further research is needed for the association between the genetic polymorphism in EPHX2 and the susceptibility to CBP.