The peroxymonosulfate (PMS)-based advanced oxidation process is considered as an effective way to remove emerging organic pollutants in the wastewater. However, the heterogeneous catalysts used for PMS activation suffers from low catalytic stability and PMS utilization efficiency. Herein, sulfur-doped cobalt ferrite loaded graphitic carbon nitride (S-CoFe2O4/CN) was firstly synthesized for PMS activation toward the sulfamethoxazole (SMX) removal. The S-CoFe2O4/CN possessed excellent PMS catalytic activity and photocatalytic activity. The first-order kinetic constant (k) of SMX degradation in the presence of visible light reached 0.3564 min−1 with high PMS utilization efficiency (78.3 %). Mechanism analysis elucidated that compared to the original CoFe2O4, sulfur doping created more oxygen vacancies, while visible light further promoted the regeneration of Co(II), Fe(II) and oxygen vacancy, the formation of high-valent iron oxo as well as the reduction of S2- oxidation. In addition, the visible light/S-CoFe2O4/CN/PMS system showed high resistance to inorganic ions, and superior catalytic stability. Both acute and chronic toxicity of treated SMX solution decreased. This study provides an effective system to remove emerging organic pollutants in the wastewater.