Four influenza virus pandemics occurred since the beginning of the 20th century. In 1918, 1957, 1968 and 2009, this disease threatened human health and social living greatly. The progress in genomic evolution of influenza virus promoted exploring pathogenic mechanism, surveilling epidemic, preparing influenza vaccine and developing anti-virus drugs. Here, we reviewed the progress in genomic evolution of influenza virus that included evolution mechanism, antigenic evolution, and anti-drug.