Our results suggested that the increased SIRT3 expression repressed the level of mito-COX-2 through PTMs of its deacetylation, mediating the inhibition of mito-COX-2 interaction with p-Drp1Ser616 and potentiating the chemosensitivity of HCC cells to platinum drugs in vitro and in vivo. This evidence concerns the gene PTGS2 and hepatocellular carcinoma.