Abstract To model and optimize the NH3-SCR performance of MnOx/γ-alumina nanocatalysts, the response surface methodology (RSM) based on a central composite design (CCD) was employed. The MnOx/γ-alumina nanocatalysts were prepared by homogeneous deposition precipitation and characterized by XRD, H2-TPR, N2 adsorption and TEM. The effect of process variables, including Mn loading, calcination temperature, concentration of O2, NH3/NO ratio and reaction temperature on NOx conversion and N2 selectivity was studied. Analysis of variance confirmed the accuracy and precision of generating quadratic models. The calcination temperature and reaction temperature had the most pronounced effects on NOx conversion and N2 selectivity, respectively. The maximum NH3-SCR performance (94.6% NOx conversion and 93.7% N2 selectivity) was predicted and experimentally validated at the optimum conditions: Mn loading 6.7 wt. %, calcination temperature 507.5 °C, concentration of O2 4.5 (vol. %), NH3/NO ratio 0.94 and reaction temperature 269.8 °C.