Size effects have been recognized to promote the catalytic activity and selectivity of metal oxide particles. So far, limited works and studies are conducted to investigate the size effect of metal oxide with the tailored shape in the selective catalytic reduction of NOx with NH3 (NH3-SCR). Herein, the MnOx-FeOy nanocage catalysts with varied scales (0.25, 0.5, 1, and 2 μm) were synthesized via a Prussian blue analogue (PBA)-derived method and used for NH3-SCR of NO. By preforming a series of the activity tests over the nanocages with different scales, the NH3-SCR activity of 0.5 μm MnOx-FeOy nanocage catalysts exhibits the highest deNOx activity in the temperature range of 80-200 °C owing to more preferable physical and chemical properties. It has been demonstrated that there is a strong interaction among Mn and Fe cations in the 0.5 μm MnOx-FeOy nanocages. Moreover, the H2-TPR and XPS analysis prove 0.5 μm nanocages exhibit excellent redox properties, which contribute to the higher conservation of NOx. Through the DFT studies, it is also demonstrated that the 0.5 μm MnOx-FeOy nanocage catalysts could provide more preferable electronic charge, which gives rise to the varied adsorption behavior of the NH3 species and NOx species compared to the nanocages with other scales. The in situ DRIFTs were also employed to evaluate the adsorption status of NH3 with NOx species over MnOx-FeOy nanocage catalysts with varied scales. Finally, the scale-activity relationship of the MnOx-FeOy nanocage catalysts and their corresponding activities are also established. The deep insight into the scale-activity relationship of the PBA-derived MnOx-FeOy nanocage catalyst paves the way for developing and designing highly efficient Mn-based catalyst at lower temperature.