Research has demonstrated that polyphenolics enact their anti-HCC activities through interference with the autophagic process, e.g., activation of Beclin-1, Atg5, Atg7, Atg9, Atg12, LC3-II, and SQSTM1, together with the modulation of PI3K/Akt/mTOR, PTEN, P38/PPAR-a, JNK/Bcl-2, ER stress, p62, p53-dependent, TGF-p receptor/Smad signaling, and YAP. The gene discussed is SQSTM1; the disease is hepatocellular carcinoma.