Influenza A virus (IAV) NS1 protein is one of the key viral factors responsible for virus-host interactions. NS1 counteracts host antiviral defense, participates in the processing and export of cellular mRNAs, regulates the activity of viral RNA polymerase and the expression of viral genes, and influences the cellular signaling systems. Multiple NS1 functions are carried out due to the interactions with cellular factors, the number of which exceeds one hundred. It is noteworthy that only two segments of IAV genome - NS and NP - did not undergo reassortment and evolved in the course of genetic drift, beginning with the pandemic of 1918 to the present. This fact may indicate the importance of NS1 and its numerous interactions with cellular factors in the interspecific adaptation of the virus. The review presents data on the evolution of the human IAV NS1 protein and analysis of the amino acid substitutions in the main structural and functional domains of NS1 protein during evolution. © 2017 Izdatel'stvo Meditsina. All rights reserved.