Swine influenza virus has a significant financial impact in pig breeding, while simultaneously raising alarms over catastrophic pandemics due to its zoonotic nature. As an obligate intracellular parasite, it relies on host factors for its replication. Understanding host-pathogen interactions is required to identify novel therapeutic targets and further design disease control. High-throughput phenotypic screens can be a powerful tool in achieving this, with CRISPR/Cas9 allowing systematic analysis of mammalian genomes. Here we developed genome-wide CRISPR/Cas9 knockout screens in porcine cells infected with influenza A virus (IAV) of human and swine origin to identify novel host dependency factors. Infected cells were sorted based on the level of IAV infection or were subjected to consequent infection challenges, and the functional relevance of genes enriched in each population was assessed using the MAGeCK pipeline. Several genes previously identified as essential for influenza infection, including SLC35A1 and ATP6AP1, were also identified as important for IAV replication in our screen. This demonstrated our approach was successful. In addition, multiple novel genes were identified as porcine IAV host-dependency factors, several of which are expressed in the same pathway. This pathway is potentially involved in disrupting IAV replication and is currently being characterised. Certain factors were shown to be species-specific. This study is the first genome-wide analysis of IAV-porcine interactions and will provide a greater understanding of genes involved in IAV replication. This data provides the basis for further gene characterisation and comparative studies with influenza A screens in human and chicken cells.