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 (<i>GSTM1</i>) null, glutathione S-transferase T1 (<i>GSTT1</i>) null, glutathione S-transferase P1 (<i>GSTP1</i>) Ile105Val, cytochrome P450 1A2 (<i>CYP1A2</i>) 734 C→A, cytochrome P450 2D6 (<i>CYP2D6</i>) <i>1934 G→A</i> 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 <i>CYP2D6 GG</i> genotype (<i>p</i> < 0.001). <i>CYP1A2</i> AA genotype was slightly higher in the infertile group <i>(p</i> = 0.056). 3. There was no association between <i>GSTT1</i> null polymorphisms and male infertility (<i>p</i> = 0.068), <i>GSTM1</i> null <i>(p</i> = 0.843) and <i>GSTP1</i> Ile105Val (<i>p</i> = 0.192) genes. <i>GSTM1</i> null genotype frequency was higher in azoospermic men <i>(p</i> = 0.009). Men carrying <i>CYP1A2</i> 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 <i>CYP2D6</i> and <i>CYP1A2</i> may play a role in idiopathic male infertility in our sample population.