Abstract: Objective To investigate the association between the single nucleotide polymorphisms (SNPs) of hsa-miR-499(miR499) and hsa-miR-608(miR608) and the risk of nasopharyngeal carcinoma(NPC) in southern Chinese population.Methods A hospital-based case-control study was conducted among 612 patients with NPC and 612 healthy participants,and the SNPs in mature region of miR499 and miR608 of the participants were genotyped by TaqMan assays.SAS 9.13 software was used to analyze the association between the miR499 as well as miR608 polymorphism and the susceptibility of NPC.Results The distribution frequencies of genotype of miR499(rs3746444 T→C)and miR608(rs4919510 C→G)were significantly different between the cases and controls (P=2.50×10^-4 and 2.71×10^-4,respectively).Compared with homozygous genotype (rs3746444 TT),the risk for NPC was increased by 44% in the carriers of variant genotypes (rs3746444 TC+CC) (adjusted odd ratioOR=1.44,95% confidence interval95%CI:1.13-1.82).And the carriers of the rs4919510(GC+GG) genotypes had a 1.58 fold risk of NPC compared to those of the rs4919510CC genotype(adjusted OR=1.58,95%CI=1.21-2.07).There was a significantly increased trend in the risk for NPC along with the increased number of variant C allele of rs3746444 as well as variant G allele of rs4919510 (P_trend=2.0×10^-4 and P=0.0001,respectively).Conclusion The findings demonstrate that miR499(rs3746444 T→C)and miR608(rs4919510 C→G) polymorphisms may contribute to an increased risk of NPC.