In the present study, HLA-Bw4-80I allele, which binds KIR3DL1 with higher affinity than the whole HLA-Bw4 allele, was observed to increase the risk of HCC incidence, indicating that NK cell activation might be involved in HBV-associated HCC development, which is consistent with our findings on HLA-C locus. Here, KIR3DL1 is linked to hepatocellular carcinoma.