It is estimated that there are millions of single nucleotide polymorphisms (SNPs) within human genome and there are likely to explain much of the genetic diversity of individuals. Hepatocellular carcinoma (HCC) is etiologically associated with hepatitis B virus (HBV) in 80% of cases, and is the dominant cause of death among HBV carriers. Among patients with chronic HBV infection, family history is a known risk factor for the development of HCC; therefore, genetic factors are likely to modify the risk of HCC. However, the genetic factors that determine progression to HCC remain mostly to be investigated. In this review, we discussed that the natural history of HBV infection and host genetic factors related to HCC, study design and target gene selection for the detection of SNPs related to the occurrence of HCC. Also, we reviewed that several SNPs or haplotypes, which were reportedly associated with increased or reduced risk of HCC occurrence in patients with chronic HBV infection. Screening of these polymorphisms might be useful in clinical practice to stratify the lower or higher risk group for HCC and might modify the design of HCC surveillance programs in patients with chronic HBV infection, if further genetic susceptibilities are identified.