Graphite felt (GF) supported cerium oxide (CeO2) composite with sulfation pretreatment (H2SO4-CeO2/GF) was prepared by the impregnation method and employed as the catalyst to activate H2O2 for degradation of isoniazid (INH). The obtained samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and X-ray photoelectron spectrum (XPS). The results showed that H2SO4-CeO2/GF had good properties in activating H2O2 for the degradation of INH. The INH removal was about 89.4% in 120 min under the following conditions: H2O2 2.94 mM, H2SO4-CeO2/GF 2.6 g/L, INH 10 mg/L, initial pH at 6.8 and temperature at 25 °C. The effects of some reaction parameters including initial H2O2 concentration, initial INH concentration, initial pH value, the catalyst dosage and reaction temperature on INH degradation were investigated. On the basis of mechanism study and intermediate analysis, the possible degradation pathway of INH was proposed. Besides, effective degradation of methyl orange (MO) and norfloxacin (NOF) also confirmed the high activity of H2SO4-CeO2/GF in activation of H2O2. The H2SO4-CeO2/GF was relatively stable, showing good application prospect.