MicroRNAs (miRNAs) are thought to play a role in cancer development. We conducted a case-control study to investigate the association between polymorphisms in miR-149C>T and hepatocellular carcinoma (HCC) risk. Duplex polymerase chain reaction with the confronting 2-pair primers were taken to genotype miR-149C>T. The association between genotype frequencies of miR-149C>T and risk of HCC was estimated as odds ratios (ORs) and 95% confidence intervals (95%CIs) using conditional regression analysis. Logistical regression analysis showed that the miR-149 CC genotype and C allele were associated with risk of HCC, with adjusted ORs (95%CI) of 2.07 (1.32-3.26) and 1.42 (1.06-2.12), respectively. Using the TT+TC genotype as a reference, individuals carrying the CC genotype were associated with non-significant increased risk of HCC, adjusted OR (95%CI) of 1.37 (0.91-2.07). Subgroup analysis showed that HBV-infected subjects carrying the miR-149 TC+CC genotype (OR=5.85, 95%CI=2.49-13.77) had an increased risk of HCC. In summary, our study found that miRNA-149C>T polymorphism is associated with risk of HCC, especially in HBV-infected patients.