The hepatitis B virus (HBV) is a widespread human pathogen that causes liver inflammation, cirrhosis, and hepatocellular carcinoma (HCC). Recent sequencing technologies have refined our knowledge of the genomic landscape and pathogenesis of HCC, but the mechanisms by which HBV exerts its oncogenic role remain controversial. In a prevailing view, inflammation, liver damage, and regeneration may foster the accumulation of genetic and epigenetic defects leading to cancer onset. However, a more direct and specific contribution of the virus is supported by clinical and biological observations. Among genetically heterogeneous HCCs, HBV-related tumors display high genomic instability, which may be attributed to the ability of HBV to integrate its DNA into the host cell genome, provoking chromosomal alterations and insertional mutagenesis of cancer genes. The viral transactivator HBx may also participate in transformation by deregulating diverse cellular machineries. A better understanding of the complex mechanisms linking HBV to HCC will improve prevention and treatment strategies.