Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world and deeply threatens people’shealth, especially in China. Techniques of early diagnosis, prevention and prediction are still being discovered,among which the approaches based on single nucleotide polymorphisms in microRNA genes (miRNA SNPs) arenewly proposed and show prospective potential. In particular, the association between SNPs in miRNA196a-2(rs11614913) and miRNA146a (rs2910164) and HCC has been investigated. However, the conclusions madewere conflicting, possibly due to insufficient sample size or population stratification. Further confirmations inwell-designed large samples are still required. In this study, we verified the association between these two SNPsand the susceptibility to HCC by MassARRAY assay in a 2,000 large Chinese case-control sample. Significantassociation between rs11614913 and HCC was confirmed. Subjects with the genotype of CT+TT or T allele inrs11614913 were more resistant to HCC (CT+TT: OR (95% CI)=0.73 (0.57-0.92), P=0.01; T allele: OR (95%CI)=0.85 (0.75-0.97), P=0.02) and HBV-related HCC (CT+TT: OR (95% CI)=0.69 (0.53-0.90), P=0.01; T allele:OR (95% CI)=0.82 (0.71-0.95), P=0.01). The affected carriers of CT or TT also tended to have lower levels ofserum AFP (P=0.01). This study demonstrated a role of rs11614913 in the etiology of HCC. Further researchshould focus on the clinical use of this miRNA SNP, so as to facilitate conquering HCC.