In many catalytic systems the structure of the catalyst plays a crucial role in the reaction especially for catalytic reduction, organic pollutant oxidation and other organic transformations. Herein, we report a template-free approach to the synthesis of multiple Au cores in CeO2 hollow spheres (MACCHS). This material was fabricated by impregnating CeO2 hollow spheres with a HAuCl4 aqueous solution. NaBH4 was then used to reduce HAuCl4 to Au nanoparticles to form multiple Au cores in the CeO2 hollow spheres. We used MACCHS as a catalyst for p-nitrophenol reduction and achieved excellent activity. The catalyst showed enhanced stability toward p-nitrophenol reduction compared with bare Au nanoparticles and CeO2 hollow spheres. This simple method to achieve multi-core-in-shell hollow structures will likely have applications in various biological, medical and energy related fields.