Efficient　and　cancer　cell-Targeted　delivery　of　photosensitizer　(PS)　and　therapeutic　protein　has　great　potentiality　for　improving　the　anticancer　effects.　Herein,　zeolitic　imidazolate　framework-8　(ZIF-8)　nanoparticles,　one　of　the　most　attractive　metal-organic　framework　materials,　were　used　for　coencapsulating　the　chlorin　e6　(Ce6,　a　potent　PS)　and　cytochrome　c　(Cyt　c,　a　protein　apoptosis　inducer);　then　the　nanoparticle　was　subsequently　decorated　with　the　hyaluronic　acid　(HA)　shell　to　form　cancer　cell-Active　targeted　nanoplatform　(Ce6/Cyt　c@ZIF-8/HA).　The　in　vitro　and　in　vivo　experiments　show　the　cancer　cell　targeting　capability　and　pH-responsive　decomposition　and　the　release　behavior　of　Ce6/Cyt　c@ZIF-8/HA.　Upon　light　irradiation,　the　released　Ce6　produced　cytotoxic　reactive　oxygen　species　for　photodynamic　therapy.　Meanwhile,　the　released　Cyt　c-induced　programmed　cell　death　for　protein　therapy.　Furthermore,　the　Cyt　c　worked　normally　under　hypoxia　conditions　and　could　decompose　H2O2　to　O2　(with　peroxidase-/catalase-like　activity),　resulting　in　synergistically　improved　therapeutic　efficiency.　These　small　molecules　and　protein　codelivery　nanoplatforms　would　promote　the　development　of　complementary　and　synergetic　modes　for　biomedical　applications.　Copyright　©　2020　American　Chemical　Society.