In this work, a simple and "signal-off" photoelectrochemical (PEC) immunosensor for prion protein detection was developed taking 3-Mercaptopropionic acid (MPA)-capped CdTe quantum dots as photocathodic materials and support for the immobilization of antibody (Ab(1)) of prion protein. In the presence of prion protein, the bioconjugates of secondary antibody (Ab(2))-gold nanoparticles-glucose oxidase (Ab(2)-AuNPs-GOx) was introduced to the electrode surface due to the specific interaction between prion and its antibodies (Ab(1) and Ab(2)). Under the addition of glucose, GOx catalyzed the oxidation of glucose and the reduction of the dissolved oxygen to in-situ generates hydrogen peroxide which could deteriorate the PEC properties of MPA-CdTe quantum dots. The consumption of the dissolved oxygen and the deterioration of the PEC properties of the photocathodic materials (MPA-CdTe quantum dots) result in the decrease of the photocurrent of the PEC platform. Under the optimal conditions, the developed PEC immunosensor could be used for sensitive assay of prion protein and showed two linear response ranges from 1 pg mL(-1) to 50 pg mL(-1) and from 50 pg mL(-1) to 1000 pg mL(-1) with the detection limit of 0.73 pg mL(-1) (3 sigma). Moreover, this method could be easily generalized for the assay of other proteins by altering the related antibodies, implying its promising applications in bioanalysis and disease diagnostics.