Hepatitis B surface antigen S2 (HBV Surface Antigen-preS2) is the smallest unit of transcriptional activator encoded by the surface gene of hepatitis B virus (HBV). It can be used as an auxiliary diagnostic reagent for hepatitis B virus infection. It exists in more than 1/3 of HBV integration units, and HBV integration units are an important factor in inducing liver cancer (HCC). HBV Surface Antigen-preS2 is also an effective regulator of apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). It is involved in promoting hepatocyte apoptosis induced by TRAIL, thereby increasing the risk of malignant transformation of human hepatocellular carcinoma cell line (HepG2).