In this work, a sulfate radical (SO4-)-based advanced oxidation process was applied to the degradation of sulfamethoxazole (SMX). In these experiments, a medium pressure UV (MPUV) lamp was employed to active peroxymonosulfate (PMS). It was found that 98% of SMX was removed by MPUV/PMS at a UV dose of 200 mJ cm-2 (3.95 μM SMX, 0.2 mM PMS, pH0 = 3.7). Direct MPUV photolysis played a remarkable role in SMX removal by MPUV/PMS process. As for the indirect photolysis, SO4- was the major reactive species under acidic and neutral conditions in MPUV/PMS system, while the hydroxyl radical (OH) became the predominant radical under alkaline conditions. The transformation products (TPs) of SMX that formed in the MPUV-only and MPUV/PMS experiments were identified, and the possible degradation pathways were proposed. Photoisomerization of the isoxazole ring was the major pathway of SMX during MPUV-only process. Hydroxylation/oxidation of the aniline and isoxazole ring was the predominant degradation mechanism of SMX by MPUV/PMS. Toxicity evaluation showed that MPUV/PMS was effective at reducing the antibacterial activity of SMX solutions, while MPUV-only was not. However, some TPs with equivalent or even higher antibacterial activity than SMX were formed during the initial degradation period in MPUV/PMS system. Ecotoxicity of SMX and its TPs was also hypothetically predicted via the ECOSAR program, and the results indicated that some TPs could be more toxic than SMX.