•A novel photon-enzyme cascade system was constructed through self-assembly.•Biocatalytic nanoflower has high HRP loading and improved activity.•The hybrid nanoflowers showed excellent degradation performance for BPA.•The HRP-CN/Cu3(PO4)2 can be an alternative to GOx&HRP cascade catalysis system. Inspired by the multi-enzymes cascade catalysis, a novel photon-enzyme cascade catalysis system described as hybrid HRP-CN/Cu3(PO4)2 nanoflowers was constructed successfully for the first time. It not only exhibits excellent immobilized enzyme enzymatic properties but also has better tolerance to extreme acid, alkali and high temperature compared with the free HRP. Moreover, the encapsulation yield of HRP reaches up to 36.2% and the residual activity after 5 cycles still has 83.6% over HRP-CN/Cu3(PO4)2 catalyst. Specifically, the HRP-CN/Cu3(PO4)2 showed excellent degradation performance for bisphenol A (BPA), which reached up to 72.98% far more than that of CN/Cu3(PO4)2 (41.89%) and HRP/Cu3(PO4)2 (4.71%). Those unique advantages are mainly owing to the introduction of photocatalyst (g-C3N4), which not only increases the encapsulation yield of HRP, but also realizes the complete mineralization of BPA. The photon-enzyme cascade catalysis system could replace the traditional system composed of glucose oxidase and horseradish peroxidase (GOx&HRP) for the harmless treatment of BPA, providing a new strategy for HRP in wastewater treatment.