In our current study, VEGFR2 inhibitor Axitinib, anti-VEGFR2 blocking antibody, and PAK1 allosteric inhibitor IPA3 were identified as efficient inhibitors for Klotho-mediated anoikis resistance and anchorage-independent growth, which paves a potential avenue for personalized therapeutic intervention of hepatoma metastasis in HCC patients with high Klotho expression. This evidence concerns the gene KL and hepatocellular carcinoma.