To further elucidate the pivotal role of PAK1 kinase activity in Klotho-induced anoikis resistance, functional alterations were analyzed after PAK1 kinase activity inhibition with kinase dead mutant PAK1 K299R cotransfection and PAK1 allosteric inhibitor IPA3 administration in Klotho-overexpressed hepatoma cells. This evidence concerns the gene PAK1 and hepatocellular carcinoma.