Objective To analyze the mutation of PreS-S region in occult hepatitis B virus(OHBV) in HBV infected persons with positive HBsAb and investigate the biological mechanisms of the special infectious model.Methods A total of 38 HB-sAb positive OBI serum samples were amplified by Nested PCR and sequenced,HBV genotype and serotype were determined.The amino acid sequences of OHBV were compared to the corresponding sequence of wild-type strains of similar genotype obtained from the GenBank database.Results PreS-S segment of 11 samples were obtained and 8 samples were sequenced successfully.Among which,5 were genotype C and 3 were genotype B.Genotype B were all serotype adw,while genotype C were 1 adw and 4 adr.The mutation rates of PreS-S region,the immunoreactive area and the major hydrophilic region (MHR) were higher in OHBV than the wild-type strains (2.6％ vs 0.8％,x2 =40.23,3.2％ vs 0.3％,x2 =52.13,3.6％ vs 0.6％,x2 =13.25,all P＜0.01) and the substitutions of I126T,Q129R,M133T,F134I,D144E,G145K in α determinant were found in OBI samples.The mutation rate of amino acids in PreS-S region was higher in genotype C than genotype B (3.5％ vs 1.2％,x2--15.98,P＜0.01),meanwhile,the mutation rates in MHR,α determinant and immunoreactive region were higher in genotype C too,but no statistical significance was attained (4.7％ vs 1.7 ％,x2 =2.96,3.6 ％ vs 2.9％,x2 =0.25,4.1％ vs 2.3％,x2 =3.59,all P ＞0.05).Conclusion Mutations in PreS-S region,especially in immunoepitope,might change the virus'immunogenicity leading to escape from immune response and cause OBI with HBsAb positive.