Here in, we investigated the association between five SNPs within MTX pathway genes consisting of MTHFR rs1801133, MTHFR rs1801131, ABCB1 rs1045642, ABCG2 rs2231142 and SLC19A1 rs1051266, with plasma MTX levels at 48 hr, toxicity of HD-MTX, as well as outcome in 74 Iranian patients with ALL. Here, ABCG2 is linked to acute lymphoblastic leukemia.