Abstract: OBJECTIVE To investigate the influence of HBV genotypes and viral variation on HBV DNA detection by Roche COBAS AmpliPrep/COBAS TaqMan 48 system and domestic fluorescence quantitative PCR system. METHODS A total of 100 patients with HBV infection in liver disease center from Mar. 2014 to Oct. 2015 were enrolled. The HBV genotype and variation of all patients were detected, and HBV DNA loads were detected using Roche COBAS AmpliPrep/COBAS TaqMan 48 system and domestic fluorescence quantitative PCR system at the same time. The differences and correlations between the results of the two methods for different HBV genotypes and viral variation were compared. RESULTS The differences of viral loads by the two methods in genotype B and C were not significant. The results of the two methods in patients without virus mutation had no significant difference, but the differences between the two methods for patients with virus mutation were significant (t=2.29, P=0.028). The correlation coefficients of the two methods for HBV DNA viral load detection in genotype B and C patients were 0.82 and 0.86,and the difference was not significant. The correlation coefficient of the two method for HBV DNA viral load detection in patients without virus mutation was 0.91, which was significantly higher than that with virus mutation (r=0.70) (Z=3.13, P<0.01). CONCLUSION For different HBV genotypes, Roche COBAS AmpliPrep/COBAS TaqMan 48 system and domestic fluorescence quantitative PCR system have a good correlation in terms of detection of HBV DNA, but HBV gene mutation may affect the accuracy of domestic fluorescence quantitative PCR system.