• P300 HAT promotes HSC activation and HCC metastasis. • HDAC3 promotes HSC activation by regulating TGFβ expression. • HDAC4 promotes HSC activation by regulating MMP9 and MMP13. • MLL1 promotes ethanol-induced HSC activation. • EZH2 promotes HSC activation by downregulating PPARγ. • JMJD2D promotes HSC activation by regulating TLR4 transcription. • SIRT6 deacetylates SMAD3 and suppresses HSC activation. • HDAC7 suppresses HSC activation by inhibiting HGF expression. • JMJD1A inhibits HSC activation by regulating PPARγ. Here, TLR4 is linked to hepatocellular carcinoma.