To reduce the NOx emission concentration of waste incineration boilers and improve the thermal efficiency of incinerators, the combustion process of a 600 t/d incineration boiler was numerically investigated. First, the influences of the secondary air injection angle, velocity and temperature on the NOx concentration at the waste incineration boiler outlet and the thermal efficiency of the incinerator were analyzed through a single factor simulation test. Then, coupling optimization of key operating parameters, including the secondary air injection angle, velocity and temperature, was conducted via the response surface design method to obtain the specific functional relationships between outlet NOx concentration, incinerator thermal efficiency, front wall secondary air injection angle, rear wall secondary air velocity and secondary air temperature, as well as the optimal operating parameters for the boiler. The results showed that when the secondary air injection angle of the front wall ranges from 68°∼80° and the secondary air injection angle of the back wall is 67°, the minimum NOx concentration is 142.23 mg/m3, and the maximum thermal efficiency of the incinerator reaches 85.51 %. When the secondary air velocity at the front wall is 42 m/s and the secondary air velocity at the back wall ranges from 42 ∼ 66 m/s, the NOx concentration at the outlet is the lowest at 140.05 mg/m3, and the thermal efficiency of the incinerator is the highest at 85.63 %. When the secondary air temperature ranges from 297.16 ∼ 309.16 K, the NOx concentration at the outlet is the lowest at 155.45 mg/m3, and the thermal efficiency of the incinerator is the highest at 84.64 %. The secondary air injection angle, velocity and temperature impose significant effects on the NOx concentration at the outlet and thermal efficiency of the incinerator. The optimal parameters, as determined in the multifactor simulation test, include a 77° secondary air injection angle of the front wall, 69 m/s secondary air velocity at the back wall, and 297.15 K secondary air temperature. Under these conditions, the NOx concentration at the outlet is 134.98 mg/m3, and the thermal efficiency of the incinerator reaches 86.11 %. This study has important guiding significance for reducing pollution and improving the efficiency of waste incineration boilers.