Abstract: Objective To estimate the relationship between the genetic polymorphisms and interaction in MPO and glutathione S-transferase M1 and T1(GSTM1 and GSTT1)and the susceptibility to childhood acute leukemia. Methods 155 Guangdong children with acute leukemia and 155 healthy children were included in the case group and the control group,respectively. MPO, GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction. A Chi-square test was used to compare the differences between the case group and the control group. Odds Ratio (OR) and 95% confidence interval (CI) were used to analyze the risk of acute leukemia in each genotype. Results MPO G-463A mutation genotype(GA and AA) was more likely to decrease risk of childhood acute leukemia(OR=0.591,95% CI:0.356-0.981, P=0.041); GSTT1 null and GSTM1 null genotype increased the risk of childhood acute leukemia 2.991-fold that of GSTT1 non-null and STM1 non-null genotype.The interaction of three genotypes showed further incident risk (OR=3.484, 95% CI:1.626-7.466,P=0.041). Conclusions The interaction of MPO G-463A GG genotype, GSTT1 null genotype and GSTM1 null genotype was related to an increased risk of childhood acute leukemia, which can be considered as an important biomarker to assess the susceptibility to childhood acute leukemia.