Abstract: Objective To investigate the distribution of hepatitis B virus(HBV) genotypes in Guangdong and explore its clinical significance. Methods Fifty-five patients with chronic active hepatitis(CAH) from Guangdong province were included in this study. HBV surface gene amplified by PCR was analyzed by restriction fragments length polymorphism(RFLP) for HBV genotyping, and the relationship of HBV genotype with clinical, serological and histological data of the patients was analyzed. Results Twenty-eight out of 55 patients were infected with HBV strains of genotype B(51.0%), 18 with genotype C(32.7%), 4 with genotype D(7.3%), 4 with HBV classified as genotype B+C(7.3%), and 1(1.8%) with HBV that did not conform to any of the genotypes from A to G. No significant differences in clinical, histological, or serological data of HBV DNA loading were detected between genotypes B and C. But in patients older than 30 years, the genotype C was accompanied by significantly higher HBV DNA loading and serum HBeAg level than genotype B(Fisher’s exact test, P=0.002). Conclusions HBV genotype B and C are the major genotypes prevalent in Guangdong Province. Genotype C is associated with the longer duration of HBeAg and higher HBV DNA level in patients older than 30 years, suggesting the higher risk of HBV genotype C infection to progress into chronic liver disease.