CYP3A5 is a member of the CYP3A gene family which metabolizes 50% of therapeutic drugs and steroidhormones. CYP3A5*3 and CYP3A5*6 polymorphisms exhibit inter-individual differences in CYP3A5 expression.The CYP3A5*3 allele (A6986G transition in intron 3) results in loss of CYP3A5 expression and the CYP3A5*6allele (G14690A transition in exon 2, leading to the skipping of exon 7) is associated with lower CYP3A5 catalyticactivity. The aim of the present study was to investigate their influence on susceptibility to chronic myeloidleukemia (CML). 265 CML cases and 241 age and sex matched healthy controls were analyzed by the PCR-RFLPtechnique. The frequencies of homozygous 3/3 genotype and CYP3A5*3 allele were elevated significantly in theCML group compared to controls (χ2=93.15, df=2, p=0.0001). With respect to clinical parameters, CYP3A5*3allele frequency was increased in patients with advanced phase of the disease (0.71) as compared to those inchronic phase (0.65). Patients without hematological response (minor/poor) had higher frequency of 3/3 genotype(54.54%) as compared to those with major hematological response (41.2%). CYP3A5*6 allele was not observed incases as well as in controls. Our study suggests that the CYP3A5*3 gene polymorphism is significantly associatedwith the risk of CML development and disease progression.