Subsequently, the activated caspase 8 cleaves activates caspase‐3, thereby executing the exogenous apoptotic pathway.[40] It has been demonstrated that ponicidin induces apoptosis by inhibiting the expression of Bcl‐2 and Survivin,[41] and that Survivin regulates apoptosis by binding to and blocking the initiator caspase 9 and effector caspase 3.[42] In our study, we found that ponicidin promotes apoptosis in HCC cells by stabilizing the formation of the Keap1‐PGAM5 complex and activating the caspase‐dependent mitochondrial apoptosis pathway. Here, CASP9 is linked to hepatocellular carcinoma.