Introduction: MicroRNAs play important roles in the development and progression of human cancers. It has been reported that miR-146a down-regulates EGFR and the NF-κB regulatory kinase interleukin-1 receptor-associated kinase 1 genes that plays important roles in lung carcinogenesis. This study was conducted to evaluate the association between a functional poly-morphism, rs2910164C＞G, in the pre-miR-146a and lung cancer risk. Material and Methods: The rs2910164C＞G genotypes were determined in 1,094 lung cancer patients and 1,100 healthy con-trols who were frequency-matched for age and gender. Results: The rs2910164 CG or GG genotype was associated with a significantly decreased risk of lung cancer compared to the CC genotype (adjusted odds ratio [aOR]=0.80, 95% confidence interval [CI]=0.66-0.96, P=0.02). When the cases were cate-gorized by tumor histology, the effect of the rs2910164C＞G genotype on the risk of lung cancer was significant in ad-enocarcinoma (aOR=0.74, 95% CI=0.58-0.93, P=0.01) and small cell lung cancer (aOR=0.68, 95% CI=0.46-0.99, P=0.04) but not in squamous cell carcinoma. Conclusions: This finding suggests that the pre-miR-146a rs1910164C＞G might be a useful marker for determining the sus-ceptibility to lung cancer and that miR-146a might be involved in the development of lung cancer.