As a recently discovered serological marker, hepatitis B core-related antigen (HBcrAg) consists of hepatitis B core antigen (HBcAg), hepatitis B e antigen (HBeAg) and p22cr. Serum HBcrAg can reflect the level and transcriptional activity of intrahepatic covalently closed circular DNA, as well as predict the natural history of patients with chronic hepatitis B or the efficacy and prognosis of nucleos(t)ide analogues and interferons, including the incidence of clinical outcomes such as relapse and functional cure, thus providing guidance for the determination of the starting point and endpoint of clinical antiviral therapy and the selection of treatment regimens. HBcrAg levels are also associated with the incidence of HBV-associated hepatocellular carcinoma(HCC), which can identify potential high-risk patients for HCC. Therefore, HBcrAg has important clinical application value in the diagnosis and treatment of chronic hepatitis B.