Seasonal epidemics of influenza A virus in the human population are a major cause of severe illness and are of high socio-economic relevance. For the design of effective anti-viral therapies, a detailed knowledge of cellular pathways perturbed by virus infection is critical. We performed comprehensive expression and organellar proteomics experiments using A549, Calu-1 and NCI-H1299 cells to identify new protein targets and cellular pathways affected by influenza A virus.