Abstract: Abstract: In this study, the recombinant retrovirus which contains the CSFV-specific shRNAs (small hairpin RNA) targeting Npro transcripts of classical swinefever virus was transfected into porcine fetal fibroblasts to drive expression of the CSFV-specific short hairpin RNA (shRNA), After stable selection, G418-resistant porcine fetal fibroblasts clones were established. Integration of the vector was proven by PCR, the viral proliferation within the cells was examined by indirect immunofluorescence assay and determination of virus titration respectively. The levels of replication of CSFV were dramatically decreased by this RNAi system in porcine fetal fibroblasts stablely transfected with the vector. Our results may be useful for therapy in CSFV and other viral infections and provide new clues for animal breeding or establishing feasible antiviral animal models.