Aim: In this study, we investigated the association between two miRNA variants and the risk of oral squamous cell carcinoma (OSCC), and explored the interaction between clinical factors in the Turkish population. Methods: In this case control study, a total of 142 subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism to analyze miR-146aG/C (rs2910164) and miR-149C/T (rs2292832) variants. Associations between OSCC risk and clinicopathological characteristics were analyzed by chi-square test Results: There was a significant difference in genotype and allele frequencies of miR-146aG/C variant between patients and control individuals. miR-146aG/C CC genotype and C allele were higher in the patient group compared to the control group (p=0.000, p=0.0001, respectively). Significant differences were also observed when the patients and the controls were compared according to CC vs GG+GC (p=0.0002) and GG vs GC+CC (p=0.002). In combined analysis, CC-CT combined genotype increased in patient group compared to controls (p=0.002), while GC-CT combined genotype increased in controls compared to patients (p=0.028), Conclusion: Our study provides evidence that miR-146aG/C variant may play an important role in susceptibility to OSCC in the Turkish population.