Pegylated interferon (PEG-IFN) is the main measure of anti-hepatitis B virus (HBV) therapy. Compared with nucleotide drugs , PEG-IFN can achieve better immune control and higher serum conversion rates for both HBV surface antigen (HBsAg) and e antigen (HBeAg). With the development in sensitive assays for quantification of HBsAg and the study of natural history of HBV infection in recent years, studies demonstrated that there is a correlation between HBsAg level and both disease progression and host immune status. Recent studies have shown that HBsAg and HBeAg levels during anti-HBV therapy are closely related to sustained virologic response and could accurately predict the efficacy of treatment. Additional work is needed to standardize and validate these assays before they can be considered to be of true clinical applicability. The research progress in this area is reviewed in the present paper.