A novel photoelectrochemcial biosensing system was fabricated based on the composition of horseradish peroxidase (HRP), flower-like CuInS2 (CIS) and graphene on indium tin oxide (ITO) electrode for detecting H2O2. The graphene layer was used as highly conductive scaffolds for electron transport from the ITO electrode to CIS. Furthermore, the flower-like CIS enhanced the multi-reflection of light and provided matrixes for the adsorption of HRP. Utilizing one-pot solvothermal method, we prepared flower-like CIS-graphene hybrid (GCIS). Electrochemical tests displayed advantage of graphene with better electron conductivity, and HRP/GCIS showed higher photoelectrochemical behavior.