Abstract: In order to screen fermented Chinese herbs medicine that can have an inhibitory effect on MSRV. In this study, the toxic effects of eight fermented herbs (L1, L2, L3, L4, L5, X1, X2 and ZHS) on EPC cells were detected by MTT method. The results showed that L1, L2, L3, X1, X2 and ZHS did not cause significant damage and toxicity to EPC cells. However L4 and L5 exhibited cell damage at a concentration of 4 mg/mL. The results were analyzed by fluorescence quantitative PCR method (qRT-PCR) screened that X1 drug (the main components were Isatidis Radix, Isatidis Radix, Radix Astragali and Almond) had good antiviral effect on MSRV; X1 drug was found to inhibit MSRV infection by qRT-PCR at the cellular level; the results of empty spot assay showed that X1 drug could reduce the virus titer of MSRV about 10 times. To evaluate the the antiviral effects of X1 drug on MSRV at the fish level, experimental groups were established including a blank control group, drug control group, attack group, prevention group and treatment group. The results showed that the treatment group could increase the survival rate of largemouth bass by 20% after treatment with X1 drug. Furthermore, qRT-PCR analysis of tissue samples demonstrated that the X1 drug notably suppressed MSRV replication in liver and spleen. The histopathological observation showed that X1 drug could inhibit MSRV-induced lesions in liver and spleen tissues. This study provides new ideas for the application of fermented herbs in aquaculture and provides a reference basis for the development of anti-MSRV drugs.