Photocathodic bioassays have shown great potential to apply in real bio-sample detection owning to their intrinsic abilities against interference from reductive species. However, the pursuit of photocathodic bioassays with excellent detection performance is still in the infancy. Herein, an advanced signal amplifier of platinum-based nanocatalyst with efficient oxygen reduction capability was explored to build a high-performance photocathodic immunoassay. The target model of carbohydrate antigen 19-9 (CA19-9, Ag) was used for describing the sensing platform. Specifically, the nontoxic Au/CuBi2O4 photocathode was first prepared by decorating Au nanoparticles on CuBi2O4 nanofilm and was used as the matrix to anchor capture CA19-9 antibody (Ab1). Platinum (Pt) nanoparticles were loaded on graphene (GR) nanosheet to form Pt/GR nanocomposite, which was utilized as signal amplifier conjugating with signal CA19-9 antibody (Ab2). When specific sandwich immunoreaction happened, the Pt/GR played the role of an efficient nanocatalyst to accelerate the reduction reaction of electron acceptor of oxygen in the electrolyte, causing evidently enhanced cathodic photocurrent signal. By incorporating this superior signal amplification strategy into the anti-interference photocathodic immunoassay, highly sensitive and specific detection of target Ag was realized. This work pioneers a new perspective for the design of advanced photocathodic bioanalysis for various targets of interest.