Molecularly imprinted composite materials (MICMs) selective to S-naproxen were prepared on the surface of mesoporous silica sphere (SBA-15) by a surface imprinting technique with S-naproxen as the template and 4-vinylpyridine as the functional monomer. As observed by SEM and pore structure analysis, the microspheres coated with the synthesized molecularly imprinted polymers have a uniform particle size, narrow size distribution and high specific surface area. The polymer layer on SBA15 can be determined by SEM, XRD and FT-IR spectroscopy. Scatchard analysis shows that two kinds of recognition sites are formed on the MICMS with the apparent binding capacities of 2.504 μmol/g and 16.680 μmol/g, respectively. Based on an isothermal binding thermodynamic investigation, the absorption to template is found to be spontaneous.