We aimed to evaluate the effect of genetic variants of the chemokine C-C motif receptor (CCR5) in the pathogenesis of oral squamous cell carcinoma (OSCC). A total of 127 patients diagnosed with OSCC and 104 healthy individuals were included in the study. The polymorphisms CCR5 59029 and CCR5-delta32 were assessed with the polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) method from peripheral blood samples of both groups. There was a statistically significant difference between the control and patient groups for CCR5 59029 A/G genotypes (P 0.05). CCR5 59029 GG and CCR5-delta32 DD + ID genotype frequencies were significantly increased in Grade II-III OSCC patients compared with Grade I-II OSCC patients. In conclusion, these results suggested that the G allele of the CCR5 59029 polymorphism might be a risk factor due to the loss of receptor function that might cause increased inflammation leading to the development of OSCC.