Fisetin (3,7,3′,4′-tetrahydroxyflavone), in HCC HepG2, Hep3B and Huh7 cells and HepG2 xenograft mouse models, promoted apoptosis by releasing Ca2+, increasing CHOP, p-eIF2α, p-PERK, cleaved caspase-3, ATF4 and induction of GRP78 exosomes to activate the ERS-mediated PERK-ATF4-CHOP signaling pathway; moreover, ERS inhibited the EMT phenomenon under radiation conditions and reversed radiotherapy resistance (Kim, 2023). Here, ATF4 is linked to hepatocellular carcinoma.