Imitating catalytic sites of natural enzymes is a promising approach to accurately improve the catalytic performances of nanozymes. Herein, inspired by the structure of natural horseradish peroxidase (HRP), three-component condensation strategy is unitized to design histidine (His) functionalized iron porphyrin covalent organic frameworks (Fe-COF-H3) nanozyme with peroxidase-like (POD-like) activity. The introduced His could form favorable microenvironment around the iron porphyrin structure, enhancing the catalytic capacity of COF nanozyme. Taking advantage of its excellent POD-like activity, Fe-COF-H3 was utilized as a carrier to immobilize urate oxidase (UOx) for the construction of enzyme-nanozyme cascade system (UOx@Fe-COF-H3). The UOx@Fe-COF-H3 was successfully applied for the colorimetric detection of uric acid (UA) in biological samples. This work not only offers a new insight to develop high-efficiency COF nanozymes, but also expands the application of COF nanozyme for the construction of enzyme-nanozyme cascade system.