The serious deactivation of denitration catalysts caused by heavy metals still a thorny issue in the practical application of selective catalytic reduction of NOx with NH3. Herein, we proposed a novel anti-poisoning strategy by designing SO42−/ZrO2 superacid supported CeO2/ZrO2 catalyst, and the effect of SO42−/ZrO2 supported CeO2/ZrO2 for PbO-resistance NOx catalytic reduction was investigated. It was worthy to note that the introduction of solid superacid SO42−/ZrO2 significantly enhanced catalytic performance over the entire temperature range, with an exceptionally high NOx removal efficiency over 98 % during 250–500 °C. When 2 wt% PbO was deposited on the fresh catalyst, the catalytic activity of CeO2/ZrO2 catalyst decreased obviously, while CeO2/ZrO2-S catalyst can still maintain a higher NOx conversion over 90 % from 275 to 500 °C. The characterization results confirmed that the introduction of solid superacid SO42−/ZrO2 enhanced the surface acidity and promoted the transformation from Ce4+ to Ce3+. The results of in situ DRIFTS implied that the Eley-Rideal (E-R) mechanism was obeyed over CeO2/ZrO2 catalyst, and both Eley-Rideal (E-R) and Langmuir-Hinshelwood (L-H) mechanisms were followed over CeO2/ZrO2-S catalyst in the SCR process. With regard to poisoned catalysts, the NH3 adsorption was inhibited to some extent, while the reaction mechanism wasn’t changed by PbO poisoning.