Abstract: Objective To determine the susceptibility of Guangzhous population to hepatitis B infection and the risk factors. Methods A stratified two-stage cluster sample survey was conducted in 12 districts or counties of Guangzhou from August to November 2008. A total of 4989 residents aged from 1 to 59 were interviewed for hepatitis B vaccination history using questionnaires, and their sera samples were collected for seromarker detection using ELISA. Results The overall prevalence of hepatitis B susceptibility in the subjects was 14.09% (95%CI: 11.84% to 16.34%). The susceptibility prevalence for people aged 7-16 years was statistically higher than that for those aged 17-59 years. It was also higher in urban areas than in suburb ones, and higher in students than in peasants. This prevalence was highly associated with close contact with hepatitis B surface antigen-positive persons, regardless of gender. Conclusion Catch-up vaccination, booster vaccination or revaccination for susceptible population will be key to improving their immunity level and reducing their susceptibility.