Abstract: There were problems such as reduced unit efficiency, blocked air preheater and excessive ammonia escape during deep peak regulation in the ultra-clean emission process of a 300 MW thermal power generating unit. The cold and hot state mapping test was carried to evaluate and diagnose the inlet flow field and the NO_x concentration in outlet section of the selective catalytic reduction（SCR） denitrification system, and the application scheme for the efficient operation of the system was proposed. Computational fluid dynamics（CFD） software was used for numerical simulation, and the solution was demonstrated by cold state physical model. The results of engineering practice application show that, the collaborative optimization can achieve a good flue gas flow distribution and maintain a low pressure drop in the denitrification system. The velocity relative standard deviation of the catalyst inlet in the first layer is reduced to 10.79%, the total pressure drop of the denitrification system is less than 600 Pa, and the net coal consumption is reduced by 0.3 g/（kW·h）, which has better energy saving and emission reduction benefits.