As more than 80% of hepatocellular carcinoma patients in Japan also suffer from hepatitis C virus infections some time in their medical history, identifying genetic aberrations associated to hepatitis C virulence in these individuals remains a high priority in the diagnosis and treatment of hepatocellular carcinoma. From the BioBank Japan Project, we acquired 480 subjects of hepatocellular carcinoma, chronic hepatitis and liver cirrhosis, and genotyped 131 clinically relevant host single nucleotide polymorphisms to survey the potential association between certain risk alleles and genes to a patient's predisposition to hepatitis C and liver cancer. Among those polymorphisms, we found 12 candidates with statistical significance to support association with hepatitis C virus susceptibility and genetic predisposition to hepatocellular carcinoma. SNPs in genes such as XPC, FANCA, KDR and BRCA2 also suggested likely connections between hepatitis C virus susceptibility and the contraction of liver diseases. Single nucleotide polymorphisms reported here provided suggestions for genes as biomarkers and elucidated insights briefing the linkage of hepatitis C virulence to the alteration of healthy liver genomic landscape as well as liver disease progression.