Influenza virus type A (IAV) infections constitute an important economic burden and raise health-care problems. Host defense mechanisms usually clear IAV infections after a few days by exploiting a variety of cellular immune responses. However, increasing the production of immunosubversive molecules is a mechanism by which viruses escape host surveillance. In this regard, the nonclassical HLA class I molecule HLA-G displays strong tolerogenic properties. We show here that several strains of IAV differently upregulate HLA-G expression, at both the mRNA and protein levels, in alveolar epithelial cells. Thus the virulence of IAV may be caused by the capability of different strains to upregulate HLA-G allowing their escape from host immune responses.