In this study, FeS2@SiO2 microspheres were firstly employed as a heterogeneous catalyst to activate persulfate (PS) for the degradation of bisphenol A (BPA) from aqueous solutions. The most relevant findings revealed that UV irradiation induced a significant improvement in the degradation of BPA by the FeS2@SiO2 microspheres/PS system. Nearly 100% of BPA degradation by the FeS2@SiO2 microspheres/PS/UV system was achieved within 120 min at reaction conditions of 1 mM PS, 0.066 mM BPA, 1.0 g/L FeS2@SiO2 microspheres and pH 3.0. A high performance on the degradation of BPA might be attributable to a synergistic effect between the PS/UV and the FeS2@SiO2 microspheres/PS catalytic processes. It was found that the BPA degradation could be inhibited by the coexisting anions like Cl-, HCO3- and PO43- to different extents at much higher concentrations, whereas NO3 had a negligible effect. Organic acids such as ethylene diamine tetra-acetic acid (EDTA) and oxalic acid (OA) would lead to an enhancement with a lower dosage, whereas a significantly negative effect was observed at much higher dosages. Radical scavenging tests revealed that the SO4 center dot- radicals prevailed over HO center dot. A total of seven intermediates during the degradation of BPA were identified by GC/MS, and a possible reaction pathway and mechanism of BPA degradation by the FeS2@SiO2 microspheres/PS/UV system was proposed. This study demonstrated a simple water treatment method involving the use of low cost natural iron minerals for organic pollutants removal.