Hepatitis B virus (HBV) infection is the main factor, which induces hepatocellular carcinoma (HCC) in Qidong high-risk area, China. To prevent HBV infection is the most important strategy to inhibit the HCC carcinogenesis. A large project was performed in Qidong area to protect newborn babies from the HBV infection that 80,000 children born between 1984 and 1990 were vaccinated. After three times of follow-up studies, 15 screened children were found to have symptoms of illness showing persistent elevation of serum glutamic-pyruvic transaminase (ALT). From these previously collected data, we found that the ALT levels of five vaccinees with negative hepatitis B surface antigen (HBsAg) were significantly higher than those of 10 vaccinees with positive HBsAg. Furthermore, with the passage of time, the difference of ALT levels between the two groups (HBsAg negative and positive groups) diminishes. After cloning and sequencing of the HBsAg "a" epitope coding sequences, we found that mutations in "a" epitope were correlated with the absence of detectable anti-HBsAg, while no mutations were seen in the anti-HBsAg positive infections. We also found that majority of point mutations were occurred in the coding sequences of the first loop structure in "a" epitope. The structure of double loop conformation in "a" epitope was conservative, and important for HBV antigenicity. These changes in a double loop conformation would escape neutralization by vaccine-induced antibody.