Silica hollow spheres were synthesized by sol-gel process using carbon microspheres as templates, and used as supports for CuO/SiO2 catalysts. The samples were characterized by TEM, nitrogen adsorption-desorption, XRD and TPR, and furthermore, the catalytic performance for CO oxidation was approached. The results indicated that the catalytic activity of CuO supported on SiO2 hollow spheres exhibited much higher as compared to that supported on commercial SiO2. Enhancement of the catalytic activity may be attributed to the fact that the unique hollow spherical texture should facilitate the formation of main active species and gas diffusion in catalysts.