Abstract: Objective To explore the CpG island methylation of human Mut S homologue 1(hMLH1) and human Mut S homologue 2(hMSH2) gene and their expressions in acute leukemia patients.Methods Reverse transcription-polymerase chain reaction(RT-PCR) and western blot were used to measure hMSH2 and hMLH1 mRNA and protein expression.Methylation-specific polymerase chain reation(MSP) technique was adopted to detect methylation of hMLH1 and hMSH2 gene in mononuclear cells of 56 acute leukemia patients and 30 healthy volunteers.Results The mRNA and protein expression levels of hMSH2 and hMLH1 in mononuclear cells of acute leukemia patients decreased significantly compared with those of healthy volunteers(P< 0.05).The frequency of promoter methylation of hMSH1and hMSH2 gene in mononuclear cells of 56 acute leukemia patients were 66.1% (37/56) and 55.4% (31/56),respectively,while those frequencies in healthy volunteers were 10.0% (3/30) and 6.7% (2/30).The differences betw een the tw o groups were statistically significant (P<0.01).There was a negative correlation between the CpG island methylation of hMLH1 and hMSH2 gene and their expressions in acute leukemia(r_hMSH2=-0.624,P=0.000; r_hMLH1=-0.589,P=0.002).Conclusion There are low expressions of hMSH2 and hMLH1 gene and high methylation of hMLH1 and hMSH2 gene in acute leukemia patients.The CpG island methylation is a factor for the low expression phenomenon of hMSH2 and hMLH1 gene in acute leukemia patients.