This paper demonstrates that silica nanoparticles were modified by the four silane coupling agents (KH-151, KH-550, KH-560, KH-570) firstly, then polystyrene/silica (PS/SiO2) composite microsphere with PS core and silica nanoparticles shell were prepared by Pickering emulsion polymerization. The characterization of optical microscope (OM), scanning electron microscope (SEM), and thermogravimetic analysis ( TGA) illustrates that these microsphere are composed of PS and silica nanoparticles. Silica nanoparticles modified by the different silane coupling agents could form the stable PS/SiO2 microsphere over 70 °C, while the unmodified silica nanoparticles are difficult to form stable PS/SiO2 microspheres at the same temperature. The PS/KH-151-SiO2 microsphere exhibits the least average particle size, while the PS/KH-570-SiO2 microsphere produces the largest. Both SEM and TGA confirm that microsphere surface exists solid nanoparticles.