The genetic variations between different individuals in the xenobiotic detoxifying enzyme activity were shown to change susceptibility to acute lymphoblastic leukemia (ALL). The current study aimed to assess the association of GSTM1 and GSTP1 genetic polymorphisms with the susceptibility of ALL. This case-control study (N=264) involved 88 Jordanian ALL children and 176 healthy controls from an ethnically homogenous Jordanian children population. The polymerase chain reaction assay was used to genotype GSTM1 (null/present) and the polymerase chain reaction–restriction fragment length polymorphism technique was also applied to detect the genetic polymorphisms of GSTP1 (Ile105Val) at the rs1695 position. The biallelic analysis revealed that there was no association between GSTM1 double-null genotype and ALL (P=0.57). However, there was a strong association between GSTP1 (Ile105Val) polymorphism genotypes and alleles within GSTP1 gene and ALL (P=0.00049 and 0.000044, respectively). A combination between GSTM1 double-null genotype and rs1695 also showed an association with ALL (P=0.042). This study showed that the rs1695 single nucleotide polymorphism within the GSTP1 gene is strongly implicated in ALL among Jordanian children with ALL. These results indicate that genetic variants of GSTP1 gene influence the risk of developing ALL in the Jordanian children of Arab ancestry.