The present study demonstrates seven phenolic compounds structures separated from water-soluble extracts of shells of Castanea mollissima, in which castanol B (1) is a new phenol derivative which reduces inflammation, inhibits cell proliferation, and increases cell apoptosis of human hepatoma cells via inhibiting TLR4–NF-κB pathway. This evidence concerns the gene NFKB1 and hepatocellular carcinoma.