Since its first origin in 1918, Influenza virus has caused the highest degree of morbidity and mortality compared with the other dreadful infections. Till date, many works were carried out on the molecular level to unveil the mystery behind this dreadful infection. In this paper, we have carried out a proteomic and structure validation analysis for the two important genes, Hemagglutinin and Neuraminidase of influenza virus isolated between 1918 to 2009. Among the subjected isolates, HA and NA protein of 2009 isolates were highly antigenic. The subcellular location of all pretense was located in the plasma membrane. Simultaneously, the structure quality checks inferred that Phyre 2 produced a better and a significant prediction for ten isolates of Hemagglutinin and Neuraminidase protein when compared to Raptor X and (PS) 2 software.