1. Glutathione S-transferases (GST) and cytochrome P450s (CYPs) are xenobiotic metabolizing enzymes participating in the protection of cell. The present study aimed to investigate the relationship between polymorphisms of glutathione S-transferase M1 (GSTM1) null, glutathione S-transferase T1 (GSTT1) null, glutathione S-transferase P1 (GSTP1) Ile105Val, cytochrome P450 1A2 (CYP1A2) 734 C -> A, cytochrome P450 2D6 (CYP2D6) 1934 G -> A and male infertility. 2. A total of 306 azoospermic or oligozoospermic infertile men and 129 normozoospermic or fertile controls were enrolled in the study. Multiplex polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism methods were used for genotyping. There was a significant relationship between male infertility and CYP2D6 GG genotype (p < 0.001). CYP1A2 AA genotype was slightly higher in the infertile group (p = 0.056). 3. There was no association between GSTT1 null polymorphisms and male infertility (p = 0.068), GSTM1 null (p = 0.843) and GSTP1 Ile105Val (p = 0.192) genes. GSTM1 null genotype frequency was higher in azoospermic men (p = 0.009). Men carrying CYP1A2 AA genotype had higher risk of infertility risk (OR = 3.14; %95 CI = 1.16-8.54) in the smoker group. 4. Our results demonstrated that polymorphisms of CYP2D6 and CYP1A2 may play a role in idiopathic male infertility in our sample population.