Tumors　have　characteristic　physiochemical　conditions　different　from　normal　tissue,　which　makes　therapy　combining　chemotherapeutic　drugs　and　tumor　microenvironment-responsive　nanocarriers　a　promising　route　for　cancer　treatment.　Here,　we　introduce　a　concept　of　integrating　catalytic　nanomedicine　and　selective　chemotherapy　for　accurate　therapy　of　early　stage　tumors　by　co-delivery　of　enzymes　and　prodrugs　into　tumor　sites　through　a　multi-responsive　nanoplatform.　The　nanoplatform　consists　of　a　polyester-hyaluronic　acid-doxorubicin　(PE-HA1000k-DOX)　prodrug　as　the　corona,　physiologically　biodegradable　silica　containing　disulfide　bonds　as　the　shell　and　hyaluronidase　(absent　in　early　stage　tumors)　as　the　core.　This　nanoplatform　is　able　to　quickly　enter　tumor　cells　through　CD44-HA　affinity.　Then,　the　esterase　and　glutathione　rich　in　tumor　cells　would　respectively　degrade　the　polyester　and　silica　to　release　HA-DOX　and　hyaluronidase　in　a　stepwise　manner.　Finally,　highly　toxic　dissociative　DOX　is　produced　through　decomposition　of　the　resulting　HA-DOX,　catalyzed　by　hyaluronidase,　for　the　apoptosis　and　death　of　the　tumor　cells.　The　properties　of　tumor-targeting　uptake,　tumor　microenvironment　responsiveness,　efficient　co-delivery　of　the　enzyme　and　prodrug,　and　intracellular　enzymatic　reaction　induced　cytotoxicity　resulted　in　a　four-fold　efficacy　against　tumor　cells　over　normal　cells,　indicating　that　our　nanoplatform　is　a　promising　material　able　to　achieve　both　selectivity　and　efficiency　concurrently　for　tumor　therapeutics.　©　The　Royal　Society　of　Chemistry.