Occult hepatitis B infection (OBI) refers to a condition where replication-competent hepatitis B virus (HBV) DNA is present in the liver, and/or HBV DNA in the blood, in individuals with serum hepatitis B surface antigen (HBsAg) negativity assessed by currently available assays. The episomal covalently closed circular DNA (cccDNA) in OBI is in a low replicative state. Viral gene expression is mediated by epigenetic control of HBV transcription, including the HBV CpG island methylation pathway and post-translational modification of cccDNA-bound histone, with a different pattern from patients with chronic HBV infection. Prevalence of OBI varies tremendously across patient populations due to numerous factors, such as the geographic location, assay characteristics, host immune response, co-infection with other viruses, and vaccination status. Apart from the risk of viral reactivation upon immunosuppression and the risk of transmission of HBV, OBI has been implicated in causing hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection, those with cryptogenic or known liver disease, and in patients with HBsAg seroclearance after chronic HBV infection. An increasing number of prospective studies and meta-analyses reported a higher incidence of HCC in HCV patients with OBI, as well as more advanced tumour histological grades and earlier age of diagnosis of HCC, compared with HCV patients without OBI. HBV DNA integration influencing hepatocyte cell cycle and tumour development, production of pro-oncogenic proteins such as HBx protein and mutated surface proteins, and persistent low grade hepatic necroinflammation contributing to liver fibrosis and cirrhosis are the proposed pathogenetic mechanisms of OBI-related HCC. Uncertainties still exist about the exact sequence of events among these mechanisms driving the development of tumour in OBI patients.