Herein, a self‐oxygenating and redox-amplifying metal-organic framework (MOF) nanoplatform is constructed by co-loading sorafenib (Sor) and plumbagin (PLB) into a surface galactose functionalized Mn-porphyrinic PCN-224(Mn) (PM) framework to afford SorPLB@Gal-PM for asialoglycoprotein receptor (ASGPR)-mediated HCC targeting. The gene discussed is ASGR1; the disease is hepatocellular carcinoma.