Developing　axial　coordination　engineering　of　single-atom　nanozymes　(SAzymes),　directly　regulating　the　axial　coordination　environment　of　the　catalytic　site,　and　optimizing　the　axial　adsorption　are　meaningful　and　challenging　for　boosting　the　enzyme-like　activities.　Herein,　the　axial　chlorination　engineering　of　SAzyme　with　the　Fe-N4Cl　catalytic　site　(Fe-N4Cl/CNCl)　was　first　proposed,　exhibiting　superior　peroxidase-like　activity　compared　to　the　traditional　Fe-N4/CN　SAzyme　with　Fe-N4　site.　The　maximal　reaction　velocity　(4.73　x　10-5　M　min-1),　the　catalytic　constant　(246.4　min-1),　and　the　specific　activity　(81　U/mg)　catalyzed　by　the　Fe-N4Cl/CNCl　SAzyme　were　4.9　times,　3.9　times,　and　2.7　times　those　of　the　Fe-N4/CN　SAzyme,　revealing　the　enormous　advantages　of　axial　chlorination　engineering　of　SAzymes　for　remarkably　improving　enzyme-like　activities.　Moreover,　the　Fe-N4Cl/CNCl　SAzyme　also　exhibited　an　enhanced　inhibition　effect　of　tumor　cell　growth　in　vitro　and　in　vivo.　The　density　functional　theory　calculation　revealed　that　the　Fe-N4Cl　site　was　more　favorable　for　releasing　center　dot　OH　radical,　lowering　the　energy　barrier　of　rate-determining　step,　and　accelerating　the　reaction　rate　compared　to　the　Fe-N4　site.　This　work　demonstrated　the　outstanding　potential　of　axial　chlorination　engineering　of　SAzymes　for　improving　enzyme-like　activities　and　practical　application　in　tumor　therapy.