In this investigation, we discovered that PFGS combined with Sor could significantly decrease activation of the NF-κB/HIF-2α/SerpinB3 pathway in H22 tumor-bearing mice and SR cells compared with a single treatment, which led to increased antitumor activity, reduced invasion ability of hepatoma cells, and perhaps prevented EMT in hepatoma cells, although further study is needed to validate this. The gene discussed is SERPINB3; the disease is hepatocellular carcinoma.