Antibiotics pose a great threat to ecological environment and human health, which should remove with an efficient innovative treatment method. Here in, a photoelectrocatalytic strategy for persulfate activation by BiVO4 photoanode had been systematically researched in this work. In the presence of PS, the degradation efficiency of sulfamethoxazole (SMX) reached to 97.3% within 100 min, whereas the kinetic rate constant was 0.0388 min− 1, which was about 7.05 times higher than no addition of PS (0.0055 min− 1). Open circuit potential (OCP), electrochemical impedance spectroscopy (EIS) and linear sweep voltammetry (LSV) were measured, suggesting that PS played a photoelectron acceptor for improving the separation of photogenerated holes and electrons and accelerating charge transfer. The radical quenching experiments and EPR tests indicated that holes and superoxide were dominant reactive oxidation species by directly oxidation pollutants. Indirect transfer pathway of S2O82− for producing hydroxyl radicals played a minor role, while only a small amount of sulfate radical was produced. Mixed pollutants with three antibiotics (ciprofloxacin (CIP), tetracycline (TC) and SMX) had been further degraded. Results showed that the degradation of SMX was inhibited in a content compared to a single pollutant, but both TC and CIP showed satisfactory removal effects, especially in natural water. Liquid chromatography-mass spectroscopy (LC-MS) was used to determine the intermediates of SMX (with 7 intermediates), CIP (with 11 intermediates) and TC (with 19 intermediates) in the PEC system. This work provides an eco-friendly and efficient method for antibiotic removal, which has good application prospect in the degradation of mixed pollutants.