Photo-assisted biofuel cell-based self-powered biosensors (PBFC-SPBs) possess the advantages of no need for external power supply, ease of sensing design, and simple instruments. In this work, a robust anti-interference PBFC-SPB for microRNA detection was constructed based on the Pt-S bond and the inorganic-organic hybridization strategy. The organic semiconductor [6,6]-phenyl-C61-butyric acid methylester@anthraquinone (PCBM@anthraquinone) served as an efficient light-harvesting material, and gold nanoparticle@Pt (AuNP@Pt) nanomaterials were immobilized on the surface via electrostatic adsorption for the binding of DNA. Notably, compared to Au-S bonds for DNA immobilization, the Pt-S bond exhibited better anti-interference ability. Ingeniously, cadmium sulfide quantum dots (CdS QDs) were close to the PCBM@anthraquinone substrate electrode to form sensitization structures, which was beneficial to enhance the photocurrent signal. Combining with the laccase-mimicking activity Cu2+/carbon nanotubes (Cu2+/CNTs) cathode, the PBFC-SPB for microRNA detection was achieved. Once the target existed, the identical sequence complementary microRNA would make DNA2/CdS dissociate and break away from the electrode, leading to a low signal. The linear detection range was 10 fM-100 pM, with the limit of determination of 2.4 fM (3S/N). The as-proposed strategy not only paves a new way for the design of photoelectrochemical biosensing but also opens a door for the construction of robust anti-interference bioassay for microRNA detection.