Homologous recombination repair (HRR) plays an important role in protection against carcinogenic factors.Genes regulating the HRR mechanisms may impair their functions and consequently result in increased cancersusceptibility. RAD 51 and XRCC3 are key regulators of the HRR pathway and genetic variability in these maycontribute to the appearance and progression of various cancers including head and neck cancer (HNC). Theaim of the present study was to compare the distribution of genotypes of RAD51 (135G/C, 172 G/T) and XRCC3(Thr241Met) polymorphisms between HNC patients and controls. Each polymorphism was genotyped using thepolymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) technique in 200 pathologicallyconfirmed HNC patients along with 150 blood samples from normal, disease free healthy individuals. We observedthat homozygous variant CC genotype of RAD51 135G/C was associated with a 2.5 fold increased HNC risk(OR=2.5; 95%CI=0.69-9.53; p<0.02), while second polymorphism of RAD 51 172 G/T, heterozygous variantGT genotype was associated with a 1.68 fold (OR=1.68; 95%CI=1.08-2.61; p<0.02) elevation when comparedwith controls. In the case of the Thr241Met polymorphism of XRCC3, we observed a 16 fold (OR=16; 95% CI=3.78-69.67; p<0.0002) increased HNC risk in patients compared to controls. These results further suggested thatRAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms may be effective biomarkers for geneticsusceptibility to HNC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.