Objective：To elucidate the distribution of HBV genotypes and subgenotypes in patients with chronic hepatitis B(CHB), hepatocellular carcinoma(HCC) and asymptomatic HBV carriers(ASC) in Shanghai and areas around Shanghai, and to analyze the role of HBV genotypes and subgenotypes in the carcinogenesis and progress of HBV-related diseases. Methods: The HBV genotypes and subgenotypes were determined in 462 HCC patients, 234 CHB patients and 110 ASCs from Shanghai and areas around Shanghai by a multiplex PCR assay. Results: Genotypes A, B, C and D and subgenotypes B2, C1 and C2 were detected. Genotype C(mainly C2, 98.5%) and B(B2, 100%) were more prevalent than other genotypes in our group. Compared with CHB group, HCC group had higher proportion of genotype C(P=0.009) and lower proportion of genotype B(P=0.045). In the patients infected with HBV subgenotypes B2 or C2, the expression of HBeAg in CHB group was significantly higher than that in HCC group(P=0.005; P=0.008), and the expression of anti- HBe was lower in CHB group(P=0.003,P=0.001).In HCC patients, expression of HBeAg in patients infected with mixture genotype was higher than that in those infected with other genotypes(P=0.016 for B2). HCC patients (aged from 40 to 60) with HBV B2 infection had lower viral load than those with C2 and genotype mixture(P=0.029, P=0.021); and patients with HBV C2 infection had lower viral load than those with genotype mixture(P=0.041). Conclusion: Subgenotype C2 is more prevalent than B2 in people living in Shanghai and areas around Shanghai. The compositions of HBV genotypes and subgenotypes are different in patients with CHB, HCC and ASCs. Co-infection with different HBV-genotypes is associated with higher viral load, expression of HBeAg and easier carcinogenesis of HCC.