In this work, the amorphous CoSx@SiO2 nanocages were hydrothermally synthesized by sulfurizing ZIF-67@SiO2 in the presence of thioacetamide (TAA). The catalytic performances of CoSx@SiO2 nanocages as heterogeneous catalysts to activate peroxymonosulfate (PMS) for the sulfamethoxazole (SMX) degradation were systematically investigated. 100% SMX was degraded within 6 min in CoSx@SiO2/PMS system, indicating that the amorphous CoSx@SiO2 nanocages exhibited outstanding sulfate radical-advanced oxidation process (SR-AOP) activity toward SMX degradation due to the regeneration of Co2+ by surficial sulfur species like S2-/S22-. The effects of PMS dosages, initial pH, SMX concentrations and co-existing ions on SMX degradation efficiency were explored in detail. The SMX removal efficiency was obviously improved in the simulated wastewater containing chloride ions (Cl-) and low-concentration bicarbonate ions (HCO3-). The residual PMS and the generated sulfate radical (SO4·-) were determined quantitatively in CoSx@SiO2/PMS system. A possible mechanism in CoSx@SiO2/PMS system was proposed based on the results of quenching experiments, X-ray photoelectron spectroscopy (XPS) analysis, electrochemical tests, and electron spin resonance (ESR). The CoSx@SiO2 exhibited good stability and reusability, in which 100% SMX removal was achieved even after five consecutive cycles. This work provided a strategy for regulating the stability of cobalt-based catalyst for efficient pollutant degradation by PMS activation.