N6-Methyladenosine (m6A) is the most abundant internal modification associated with eukaryotic mRNAs, and is reported in many viral RNAs recently. Viral epitranscriptomics is a newly emerging area which focus on functionally relevant post transcriptional modifications of viral transcripts that regulates viral gene expression, life cycle and host immune response. Influenza virus (IAV) is the first virus that has been identified with m6A marks; however, regulatory potential of this epigenetic marks has not been explored in depth. The m6A modification is co-transcriptionally added to nuclear pre-mRNAs by m6A writers, read by cytoplasmic m6A readers, and can be reversed by m6A erasers. Here in this study, we aim to investigate the role of YTHDF2, one of the YTH domain containing m6A reader protein in regulating IAV life cycle. We have found YTHDF2 inhibits avian influenza virus replication in vitro. To explore the role of m6A marks, we mapped the m6A motifs in IAV viral RNA and engineered recombinant IAV by deleting or adding m6A marks in the haemagglutinin gene. We have also cloned different regions of YTHDF2 to identify the region involved in interaction with m6A. Furthermore, we have found YTHDF2 interactions with other host factors that modulates virus gene expression. Insights into influenza virus-regulated epitranscriptomics and host virus interplay reveals unique mechanism in regulation of virus and host immune response.