Swine influenza virus (SIV) poses a significant threat to the pig industry and public health safety due to rapid viral evolution and potential interspecies transmission. Identifying the key host factors that involved in viral replication can not only provide new insights into the regulatory mechanism of viral replication, but also provide theoretical support for the development of new antiviral therapeutics. Here, the Pre-mRNA cleavage complex II protein Pcf11 (PCF11) was revealed to promote the proliferation of SIV and other influenza viruses. Mechanically, PCF11 promoted the synthesis of viral mRNA and the assembly of vRNP, thus facilitating the transcription and replication of viral genome. Furthermore, PCF11 can interact with viral NP proteins to promote the polymerase activity of SIV. Additionally, PCF11 was revealed to negatively regulate the IFN-β signaling pathway, facilitating the replication of RNA viruses. In conclusion, this study emphasizes that PCF11 promotes SIV proliferation by regulating viral genome replication, transcription, and innate immune responses, thus providing a potential target for developing antiviral therapeutics.