We report here a novel photocurrent polarity switching strategy for a photoelectrochemical immunoassay driven by the covalent reaction between fullerenol (COH) and chloranilic acid (CA). The sensitive detection of interleukin-6 is achieved by using CA-encapsulated liposome as the label and COH-coated ZnO as the photoactive material, with a detection limit of 1.0 fg mL-1.