Therefore, our study aimed to investigate the modulatory effect of cucurbitacins D, I, and E, isolated from the Ecballium elaterium plant, on the PI3K/Akt/NF-κB pathway and to assess their potential antiinflammatory and cytotoxic effects by comparing them with sorafenib, a drug used in the treatment of HCC. This evidence concerns the gene NFKB1 and hepatocellular carcinoma.