The effect of SO2 on the selective catalytic reduction of NOx by NH3 over V2O5-0.2CeO2/TiO2-ZrO2 catalysts was studied through catalytic activity tests and various characterization methods, like Brunner−Emmet−Teller (BET) surface measurement, X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray fluorescence (XRF), hydrogen temperature-programmed desorption (H2-TPR), X-ray photoelectron spectroscopy (XPS) and in situ diffused reflectance infrared Fourier transform spectroscopy (DRIFTS). The results showed that the catalyst exhibited superior SO2 resistance when the volume fraction of SO2 was below 0.02%. As the SO2 concentration further increased, the NOx conversion exhibited some degree of decline but could restore to the original level when stopping feeding SO2. The deactivation of the catalyst caused by water in the flue gas was reversible. However, when 10% H2O was introduced together with 0.06% SO2, the NOx conversion was rapidly reduced and became unrecoverable. Characterizations indicated that the specific surface area of the deactivated catalyst was significantly reduced and the redox ability was weakened, which was highly responsible for the decrease of the catalytic activity. XPS results showed that more Ce3+ was generated in the case of reacting with SO2. In situ DRIFTS results confirmed that the adsorption capacity of SO2 was enhanced obviously in the presence of O2, while the SO2 considerably refrained the adsorption of NH3. The adsorption of NOx was strengthened by SO2 to some extent. In addition, NH3 adsorption was improved after pre-adsorbed by SO2 + O2, indicating that the Ce3+ and more oxygen vacancy were produced.