These data suggest that Klotho/VEGFR2/PAK1 signal inhibition with VEGFR2 inhibitor Axitinib, or anti-VEGFR2 blocking antibody, or PAK1 allosteric inhibitor IPA3 administration might be used as potential therapeutic interventions with progression and metastasis of HCC patients, which awaits further clinical investigations. This evidence concerns the gene KL and hepatocellular carcinoma.