For chronic hepatitis B (CHB) therapy, a new concept named “functional cure” that is defined as loss of the serum hepatitis B virus surface antigen (HBsAg) is proposed and pursued clinically in recent years. However, this goal is hard to be approached by current available antiviral therapy. To understand the performance on reduction of HBsAg in antigen-antibody complex therapeutic hepatitis B vaccine (YIC)-treated CHB patients, a pooled analysis was carried out based on phase Ⅱb and Ⅲb trials. After treatment and withdrawal follow-up, it showed that those who achieved HBV e antigen (HBeAg) seroconversion experienced a decrease of HBsAg level up to 0.95log₁₀IU/mL, which was significantly higher than 0.32log₁₀IU/mL of those who did not achieve HBeAg seroconversion (P<0.01). Conversely, the reduction was 0.49log₁₀IU/mLand 0.36log₁₀IU/mL among HBeAg seroconverted and non-converted patients in control group treated with aluminum hydroxide adjuvant (Alum). During treatment period, alanine aminotransferase (ALT) flare was more frequently detected among those patients who reached a HBsAg reduction of >1.0log₁₀IU/mL in YIC group, rather than in Alum group. Predictors of HBsAg reduction were HBeAg seroconversion, B genotype of HBV infection, ALT flare occurred during treatment, and high serum HBsAg levels at baseline. Since specific adaptive immune response elicited by YIC has been demonstrated in some CHB patients, to further improve the rate of “functional cure”， the “sandwich” strategy (antiviral treatment ＋ HBsAg monoclonal antibody ＋ YIC) might be considerable.