Copper sulfide (CuS), an excellent photoactive material, is introduced into a paper-based photoelectrochemical (PEC) immunosensor for the first time using an in situ electron donor producing approach. ZnO nanoflakes (ZNF) with a large surface area are first electrodeposited onto a gold-paper electrode, and then functionalized with CuS via a simple hydrothermal and ion exchange method. The recombination process of electron-hole pairs in CuS is prevented since the energy levels between ZnO and CuS are matched well, resulting in a high PEC performance. The glucose oxidase (GOx) and signal antibodies co-labeled nanoporous gold (NPG) is then introduced into the immunosensor via sandwich immunoreactions. On the basis of the catalytic chemistry of GOx to produce in situ H 2 O 2 for electron donation, an enhanced photocurrent was achieved. By coupling the brilliant properties of CuS/ZNF, a modified gold-paper electrode with amplified electron donor production through NPG, a sensitive PEC immunosensor for carcinoembryonic antigen (CEA) analysis is proposed. The immunosensor displayed a linear response to CEA in the range from 2 pg mL À1 to 100 ng mL À1 with a relatively low detection limit of 0.7 pg mL À1 . The proposed immunosensor exhibited good performance, which has a promising prospect in clinical diagnosis.