Metalloenzymes　are　promising　anticancer　candidates　to　overcome　chemoresistance　by　involving　unique　mechanisms.　To　date,　it　is　still　a　great　challenge　to　obtain　synthetic　metalloenzymes　with　persistent　catalytic　performance　for　cancer-specific　DNA　cleavage　and　operando　imaging.　Here,　an　artificial　metalloenzyme,　copper　cluster　firmly　anchored　in　bovine　serum　albumin　conjugated　with　tumor-targeting　peptide,　is　exquisitely　constructed.　It　is　capable　of　persistently　transforming　hydrogen　peroxide　in　tumor　microenvironment　to　hydroxyl　radical　and　oxygen　in　a　catalytic　manner.　The　stable　catalysis　recycling　stems　from　the　electron　transfer　between　copper　cluster　and　substrate　with　well-matched　energy　levels.　Notably,　their　high　biocompatibility,　tumor-specific　recognition,　and　persistent　catalytic　performance　ensure　the　substantial　anticancer　efficacy　by　triggering　DNA　damage.　Meanwhile,　by　coupling　with　enzyme-like　reactions,　the　operando　therapy　effect　is　expediently　traced　by　chemiluminescence　signal　with　high　sensitivity　and　sustainability.　It　provides　new　insights　into　synthesizing　biocompatible　metalloenzymes　on　demand　to　visually　monitor　and　efficiently　combat　specific　cancers.