Background: Genetic variation influencing individual susceptibility to chemical carcinogens is one of the main factors leading to cancer development. The glutathione S-transferases (GSTs) are a family of enzymes belonging to phase II enzymes involved in detoxification of xenobiotics. A significant relationship is observed between the risk of developing cancer and genetic polymorphisms within GSTs. Methods: In this study, we investigated the influence of inherited GSTP1 (Ile105Val) gene polymorphism on the susceptibility to CML in Egypt in 40 CML patients (20 children and 20 adults), together with 40 healthy controls using a [PCR-RFLP] assay. Results: We found that the mutant type (IIe/Val, Val/Val) was significantly higher in CML patients (67.5%) compared to controls (35%) (p = 0.004); [odds ratio 3.9; 95% CI: 1.5 - 9.7]. The mutant type was associated with more advanced phases in disease and with both worse hematological and cytogenetic responses when compared to the wild type (p = 0.03, p = 0.05, and p < 0.001, respectively). Conclusion: GSTP1 (Ile105Val) gene polymorphism conferred a significant association with increased risk of CML and is associated with worse prognosis. Further studies on the functional consequences of this genetic polymorphism would pave the way to declare its role in the pathogenesis of CML or as a possible predictor for response to therapy.