A series of well-dispersed CeMnO_x hollow nanospheres with uniform diameter and thickness were synthesized by a novel approach combining the template method and interfacial reaction. A SiO₂ template was used as a hard template for preparation of SiO₂@CeO₂ nanospheres by solvothermal reaction. SiO₂@CeMnO_x could be formed after KMnO₄ was reacted with SiO₂@CeO₂ by interfacial reaction between MnO₄⁻ and Ce³⁺. Among all the prepared catalysts, CeMnO_x-3 with a moderate content of Mn (15 wt%) exhibited the lowest temperature for complete combustion of toluene (280 °C). Moreover, it showed high stability for 36 h with toluene conversion above 97.7% and good water tolerance with 5 vol% H₂O. With characterization, we found that the reaction between Ce and Mn in the Ce–Mn binary oxides gave rise to increased Ce³⁺ and oxygen vacancies, which led to the formation of enhanced reducibility and more surface-absorbed oxygens (O₂²⁻, O²⁻ and O⁻), and improved the catalytic performance further.