Objective Adopting serology assay-fluorescent antibody to membrane antigen (FAMA) as "gold standard" , sero-prevalence status of varicella-zoster virus (VZV) infection was investigated, in Guangzhou. Methods FAMA test was established with VZV infected human embryo fibroblasts as antigens and fluorescein isothiocyanate(FITC) labeled goat anti-human IgG as the secondary antibody. Sensitivity and specificity of the assay were evaluated. The sero-prevalence of anti-VZV IgG in 592 serum specimens randomly collected from a clinical laboratory, was analyzed with FAMA. Results Data from FAMA test showed no cross-reaction with other Herpesviruses when it was used to detect VZV antibodies. The overall prevalence of VZV antibody was 76.52%. Age-specific prevalence rates of VZV antibody in different age groups as: 1-3, 4-6, 7-13, 14-19, 20-29, 30-39, 40-49, ≥50, were found to be 14.67%, 51.56%, 73.91%, 91.26%, 92.78%, 95.65%, 98.11% and 100%, respectively.The sero-prevalence of 1-3 age group appeared the lowest but rose sharply with the increase of age but showing no association with gender. Conclusion Our data indicated that VZV infection occurred in early childhood, in Guangzhou, suggesting that the primary recipients of VZV vaccine should be under the 1-3 age group. Additional subjects for vaccination would be children above 3 years old with no history of VZV infection, and serology test negative for VZV. The assay was validated by its excellent specificity and could be used as the first choice in the detection of protective antibodies against VZV infection.