Cellular proteins that support influenza virus infection represent potential therapeutic targets. Cytoplasmic egress intermediates of influenza A/WSN/33 were isolated and shown to be associated with the cellular enzymes peroxiredoxins-1 (Prdx-1) during glycerol gradient fractionation. Prdx-1 also co-localizes with influenza NP at the cell periphery late in infection. Knock-down or knockout of Prdx-1 expression inhibit influenza A replication. Inhibition of replication is not correlated with defects in initiation of infection or mRNA expression, but is correlated with inhibition of accumulation of viral proteins and vRNAs.