Cisplatin　(DDP)　is　a　prevalent　chemotherapeutic　agent　used　in　tumor　therapy,　yet　DDP-induced　acute　kidney　injury　(AKI)　severely　limits　its　clinical　application.　Antioxidants　as　reactive　oxygen　species　(ROS)　scavengers　can　circumvent　this　adverse　effect　while　leading　to　the　decrease　of　efficacy　to　tumor.　Herein,　we　report　ultrasmall　ruthenium　nanoparticles　(URNPs)　as　switchable　ROS　scavengers/generators　to　alleviate　DDP-induced　AKI　and　improve　its　therapeutic　efficacy.　In　the　physiological　environment　of　the　kidney,　URNPs　mimic　multi-enzyme　activities,　such　as　superoxide　dismutase　and　catalase,　effectively　protecting　the　renal　cell　and　tissue　by　down-regulating　the　increased　ROS　level　caused　by　DDP　and　alleviating　AKI.　Specifically,　URNPs　are　oxidized　by　high　levels　of　H2O2　in　the　tumor　microenvironment　(TME),　resulting　in　the　generation　of　oxygen　vacancies　and　Ru3+/Ru4+　ions.　This　unique　structure　transformation　endows　URNPs　to　generate　singlet　oxygen　(1O2)　under　laser　irradiation　and　hydroxyl　radicals　(∙OH)　through　a　Fenton-like　reaction　in　tumor　cell　and　tissue.　The　simultaneous　generation　of　multifarious　ROS　effectively　improves　the　efficacy　of　DDP　in　vitro　and　in　vivo.　This　TME-responsive　ROS　scavenger/generator　acts　as　an　adjuvant　therapeutic　agent　to　minimize　side　effects　and　improve　the　efficacy　of　chemotherapy　drugs,　providing　a　new　avenue　to　chemotherapy　and　facilitating　clinical　tumor　therapy.　Graphical　Abstract:　(Figure　presented.).　©　The　Author(s)　2024.