Objective To investigate the combination inhibitory effect of the important components of baicalein and wogonin of suduxing, a new anti-hepatitis B virus (HBV) Chinese herbal on entecavir (ETV)-resistant mutant virus, and to find the optimal ratio of the two components. Methods The ETV-resistant HBV stable replication cell line HepG2. A64 was divided into the baicalein group, the wogonin group, the combined drug group, and the control group, respectively. According to the toxicity test results of baicalein and wogonin, cells in the the baicalein group were treated with baicalein at 4, 8, and 16 μ, mol/L, respectively, and recorded as the B4, B8, and B16 groups; cells in the wogonin group were treated with wogonin at 3, 6, and 12 μ, mol/L, respectively, and recorded as the W3, W6, and W12 groups. The first part of cells in the combined drug group was treated with baicalein (4 μ,mol/L) and the wogonin of different concentrations ( 3, 6, 12 μ,mol/L), respectively, and recorded as B4 + W3, B4 + W6, B4 + W12 groups ; the second part of cells in the combined drug group were treated with baicalein (8 μ,mol/L) and wogonin of different concentrations ( 3, 6, 12 μ, mol/L), recorded as B8 + W3, B8 + W6, B8 + W12 groups; the third part of cells in the combined drug group were treated with baicalein ( 16 μ,mol/L) and wogonin of different concentrations ( 3, 6, 12μ, mol/L), recorded as B16 + W3, B16 + W6, B16 + Wl2 groups. The cells in the control group were treated with an equal amount of DMEM medium. Cells of each group were cultured for 96 h, the HBV DNA in the cell supernatant was detected by the PCR-fluorescent probe "one-tube method", and the HBV DNA inhibition rate was calculated; the HBsAg in the cell supernatant was detected by the double antibody sandwich method, and the HBsAg inhibition rate was calculated; HBV total DNA and HBV covalently closed circular DNA ( cccDNA) were detected by fluorescence quantitative PCR method, and the inhibition rate of HBV total DNA and HBV cccDNA was calculated. The Q method of Jin Zhengjun was used to evaluate the synergism between baicalein and wogonin. Results The inhibition rates of HBV DNA, HBsAg in the cell supernatant, intracellular total DNA and cccDNA of the baicalein group, the wogonin group, and the combined drug group were higher than those in the control group ( all P < 0.05 ). The HBV DNA inhibition rate in the cell supernatant of the combined drug group was higher than that of each single drug ( all P <0.05), the B16 + W3 group had the highest Q value (0.970). The HBsAg inhibition rates in the cell supernatants of the B8 + W12, B16 + W3, and B16 + W12 groups were higher than that of each single group ( P < 0.05) The Q value of the B16 + W3 group was the highest (0.886). The inhibition rates of intracellular total HBV DNA of the combined drug group were higher than those of the baicalein group and wogonin group with the same drug concentration ( all P < 0.05) . The B16 + W3 group had the highest Q value ( 1.183). The inhibition rates of HBV cccDN A in the cells of B16 + W3, B16 + W6, and B16 + W12 groups were higher than those of the baicalein group and wogonin group with the same drug concentration, of which the B16 + W3 group had the highest Q value (0.972). Conclusions The baicalein and wogonin have inhibitory effects either individual or combination on ETV-resistant HBV DNA, HBV cccDNA, and HBsAg in HepG2. A64 cells. Inhibition effect of baicalein combined with wogonin is stronger than that of each single drug with the same drug concentration. The combination of 16μ, mol/L baicalein and 3μ, mol/L wogonin (5:1) has the optimal inhibitory effect. [ABSTRACT FROM AUTHOR]