Head and neck squamous epithelial cell cancer (HNSCC), the world's fifth most common type of cancers, is associated with short life expectancy and high death rates if not detected in early stages. The aim of this study was to investigate hRRM1 and p53R2 gene polymorphisms by using real-time PCR technique in patients with head and neck cancer. In total, 87 patients with head and neck malignancies and 87 control group who have not any malignancies were included in the study between January 2011 and February 2012 in Istanbul University Faculty of Medicine Department of ORL. In the study, real-time PCR was used to detect hRRM1 (rs12806698 C/A) and p53R2 rs2290707 G/T) gene polymorphisms in Turkish HNSCC patients and healthy individuals. Genomic DNA isolation was performed according to the kit protocol with spin column. LightCycler 1.5 system was used to perform SNP genotyping using hybridization probes consisting of 3'-fluorescein and a 5'-LightCycler Red labeled pair of oligonucleotide probes. There were significant differences in the distribution of hRRM1 genotypes. Frequency of individuals with hRRM1 AA genotype was higher in patients with less differentiation when compared with well differentiation [p 0.025, Fisher's exact test, odds ratio (OR) 0.140, 95 % confidence intervals (CI) 0.024-0.797]. It is observed that A allele carriers have nearly twofold risk for development of the disease (p = 0.022; chi(2) 5.24; OR 2.02, 95 % CI 1.10-3.72).