A series of tem-responsive and protein-resistance property silica-di-block polymers SiO2-g-PMMA-b-P(PEGMA) hybrids are synthesized with methyl methacrylate (MMA) and poly (ethylene glycol) methyl ether methacrylate (PEGMA) by the surface-initiated atom transfer radical polymerization (SI-ATRP). The morphology in tetrahydrofuran (THF) solution, lower critical solution temperature (LCST), surface morphology, bovine serum albumin (BSA)-resistance property, and thermal stability of nanoparticles were analyzed. The results of 1H-NMR, GPC, and TEM prove that the silica-di-block hybrids have been obtained. The silica-di-block hybrids shows the LCST (52–64 °C) in aqueous solution. The hybrid films casted by THF present distributed uniform granular bulges and the film surface is relatively smooth (Ra = 15.4 nm ~ 10.5 nm). The results of QCM-D showed that only a small amount of BSA protein(△f = 18.6 ~ 11.8 Hz) was adsorbed on the surface of the films. The result of XPS also demonstrated that only a small amount of BSA protein was absorbed onto the surface of the film (N% = 1.86). The TGA analyses indicate that the thermal decomposition temperature of hybrids is 288 °C. Thus, it is suggested that the hybrids are served as a suitable coating with BSA resistance property and thermal stability.