A series of MnxCe1-xO delta/3DOM-m SiO2 catalysts with different Mn0.5Ce0.5O delta loadings and different x values were designed and successfully prepared by a very simple method. The as-prepared catalysts, which contain three-dimensionally ordered macroporous (3DOM) structure embedded with ordered mesoporous structure, exhibit high catalytic activity and good stability for soot combustion. The good catalytic performances of as-prepared catalysts are owing to facilitated soot transport through the macroporous structure and synergistic effect between Mn and Ce for the activation of gas molecules (NO and O-2) within the mesoporous structure. In addition, the sulfur and water tolerance of as-prepared catalysts were tested and the reasons for sulfur and water tolerance also well illustrated. The probable soot combustion mechanisms are proposed based on the characterization results and DFT calculation. More importantly, this work demonstrates the rational design and facile preparation of highly efficient catalysts for reactions between large solid particles and small gas molecules.