Hepatitis B virus (HBV) infection remains a significant public health problem worldwide. Current therapies have made great progress for the controlling of liver disease progression and its detrimental clinical sequelae. However, the lack of curativeness of current antiviral therapies is attributed to their inability to eliminate HBV covalently closed circular DNA (cccDNA), which serves as a key factor in maintaining the persistent form of the viral genome and transcription template for virus reproduction, leading to chronic hepatitis B patients requiring long-term medication or relapse after treatment. Previous studies have confirmed that the transcription from HBV cccDNA is regulated by epigenetic mechanism, including cccDNA methylation, histone modification, microRNAs, chromatin remodeling and other aspects. In this review, we summarize the latest progress on epigenetic regulation of HBV from the related aspects.