Consistent with our hypothesis, inhibition of Rac1 activity by knockdown or NSC23766 treatment was associated with increased Rac1 phosphorylation and reversed AKT/NF-κB signaling in both sorafenib-resistant and sorafenib-sensitive HCC cells, consequently enhancing the antiproliferative effect of sorafenib. Here, AKT1 is linked to hepatocellular carcinoma.