The aim of the present study was to investigate the association of single nucleotide polymorphisms (SNP) of the microRNA-146a (miR-146a) genes with the risk of nonsmall cell lung cancer (NSCLC). The genotyping of miR-146a rs2910164 polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that CC genotype and C allele distribution in the NSCLC patient were significantly higher than that of the controls (P = 0.03 and 0.03, respectively). No significant differences were found between the two subgroups when stratified by clinical characteristics including age, sexual, smoke status, histological type, lymph node metastasis and clinical stage. In addition, the expression of miR-146a was detected by the Taqman real-time PCR. It demonstrated that the miR-146a expression was significantly decreased in NSCLC patients compared with that of nonmalignant lung tissues (P = 0.01). In addition, the miR-146a expression of CC genotypes subgroup was significantly decreased than of GC/GG genotype subgroup in tumor tissues (P = 0.0022). It confirmed that the SNP rs2910164 could functionally affect the miR-146a expression levels. In conclusion, it showed that the rs2910164 polymorphism of miR-146a is associated with the risk of NSCLC in the Chinese population.