Lung cancer is still the most common cancer worldwide in terms of the number of newly diagnosed cases and mortality rate. The expression of miR-146a was reduced in mesenchymal-like lung cancer cell lines. The overexpression of miR-146a induced a marked reduction of the mesenchymal marker and increase in the epithelial marker in lung cancer cell lines. The current study investigated the association of miR-146a genotypes and lung susceptibility in a Tehran population to determine the visibility of using RFLP-PCR genotype. The results revealed a significantly higher frequency of miR-146a CG and CC genotypes (p =0.01 and p=0.008, respectively) in patients compared with the control group. Those with the miR-146a GC and CC genotypes had an increased risk for developing lung cancer (OR=1.9; 95% CI: 1.1-3.3 and OR=4.1; 95% CI: 1.5-12.3, respectively). Moreover, the frequency rates of miR-146a CC genotype and C allele were significantly higher in patients than in the controls (p =0.006 and p=0.000, respectively).