A growing body of evidences suggests that hydrogen peroxide (H2O2) plays an effective role in the regulation of multifarious physiological processes. Development of sensitive probes for H2O2 is an urgent hotspot. In this work, we recommended a coenzyme A (CoA)-mediated gold coordination polymer (CoA-Au(I) CP) for sensitive electrochemical detection of H2O2. The biosensing mechanism is based on the following highlights: the formation of an unordinary structure with -thiol-Au(I)- repeated units derived from thiol in CoA; an extraordinary interaction between graphene (GO) and CoA-Au(I) CP due to massive adenines. A potential application of the resultant CoA-Au(I) CP as a novel sensing platform to monitor H2O2 is investigated. Such CoA-Au(I) CP-based sensor exhibited an excellent electro-catalytic property for H2O2 reduction. The steady-state current response increases linearly with H2O2 concentration from 0.1 to 300 mu M with a low detection limit of 0.02 mu M. Importantly, the proposed electrochemical biosensor has shown a new perspective for detection of H2O2 levels in human real samples and that released from human cervical cancer cells with satisfactory results. This novel CoA-Au(I) CP nanomaterial may provide a cost-efficient, robust and high-sensitive platform for detecting various species involving H2O2-generation reactions for biomedical applications.