Hepatitis B virus (HBV) is a double-stranded DNA virus, causing the widely known disease hepatitis B. Besides, infections with HBV can result in cirrhosis and hepatocellular carcinoma. HBV gene encodes several products of small (HBs), middle (MHBs), and large (LHBs) surface protein, sharing a common open reading frame (ORF). Among them, HBs of 226 amino acids is a major component of the viral envelope. MHBs has an additional 55 amino acids, known as pre-S2, located at the N-terminus of HBs, and LHBs has extra 119 amino acids, named pre-S1. Pre-S1 and S2 constitute the region of pre-S, and pre-S2 plays a role in translocation of the virus into host cells. Furthermore, pre-S protein may involve virus assembly and virus entry into host cells. And the presence of pre-S in serum has been thought to associate with active viral replications. Infectious particles of hepatitis B virus (HBV) are known as Dane particles or 42-nm particles, which consist of viral nucleic acids within core particles enveloped by 3 virus-coded proteins, large S (LS), middle S (MS), and major S (SS) surface proteins. These proteins are embedded in a lipid bilayer derived from the host cell. SS composed of 226 amino acids is a predominant component in these proteins and it is often called HBV surface antigen (HBsAg). Half of SS is in the glycosylated form (gp27), while the others are in the nonglycosylated form (p24). MS has an extra extension of 55 amino acids (pre-S2) at the N-terminus and shares a common terminal with SS. There are three forms of MS comprising p30, gp33, and gp36, based on the extent of glycosylation. Also, LS is coterminal with SS and MS, characterized by an extension polypeptide (pre-Sl) at the N terminus of MS. And there are glycosylated (gp42) and nonglycosylated (p39) forms of LS.