A three-dimensional model that combined the selective catalytic reduction (SCR) of NO with ammonia and SO2 oxidation reactions over monolith honeycomb catalyst was established to study the effects of catalyst structure and operating parameters on NO reduction and SO2 oxidation. The model was to proved to be valid by experimental data. Simulation results showed that the SCR reaction only took place within a thin layer (ca. 0.2 mm) of the catalyst wall surface, whereas SO3 generated via SO2 oxidation accumulated throughout the entire wall. The effects of typical operating parameters, i.e., space velocity, temperature, feed concentrations of NO, NH3 and SO2 were studied. Temperature and gas velocity were found to be the major influencing factors on SO2 oxidation. A strategy for monolith catalyst struction optimization, i.e., using thin-walled catalyst was proposed on the basis of these results.