Multi-modal　synergistic　therapy,　especially　the　integration　of　near-infrared　laser　phototherapies　and　chemotherapy,　is　often　sought　after　owing　to　its　minimal　invasiveness,　low　side　effects,　and　improved　anticancer　therapeutic　efficacy.　Herein,　CuS　nanoparticles　were　first　coated　with　zinc　phthalocyanine　derivant　(Pc)-functionalized　mesoporous　silica　(mSiO2-Pc)　to　achieve　a　drug　delivery　system　(CuS@mSiO2-Pc)　with　photothermal/photodynamic　therapy.　Chemical　drug　DOX　was　subsequently　loaded　for　chemotherapy,　and　hyaluronic　acid　(HA)　was　employed　as　a　covering　material　with　cancer　targeting.　The　as-obtained　CuS@mSiO2-Pc(DOX)@HA　nanoparticles　were　nano-sized　with　good　biocompatibility,　effective　DOX　loading,　and　controllable　DOX　releasing.　Expectedly,　this　multifunctional　nanoplatform　exhibits　effective　generation　of　reactive　oxygen　species　and　hyperthermia　upon　the　near-infrared　laser　irradiation.　Most　importantly,　the　nanoparticles　were　targeted　into　4T1　cells　and　showed　significantly　remarkable　cytotoxicity　under　near-infrared　laser　irradiation,　proving　their　synergistic　therapeutic　efficacy.　Therefore,　this　targeted　drug　system　based　on　CuS　with　synergistic　photothermal　therapy/photodynamic　therapy/chemotherapy　has　great　application　prospects　in　clinical　anticancer　treatment　for　triple　negative　breast　cancer.　©　2022　American　Chemical　Society.