The synthesis of a poly(ethylene glycol) (PEG)-grafted surface-reactive random copolymer and its self-assembled structure on Si/SiO2 substrates for construction of nonbiofouling surfaces are reported. The copolymer, poly(TMSMA-r-PEGMA), which is comprised of an "anchor part" (trimethoxysilane) and a "function part" (PEG), was synthesized by a radical polymerization reaction. The copolymer spontaneously formed monolayers on Si/SiO2 wafers with average thicknesses of 11Angstrom. Tapping mode atomic force microscopy (AFM) revealed that the surface of the polymer monolayers was smooth with an average roughness of 1.3Angstrom (root-mean-square). The protein resistance of the polymer monolayers on Si/SiO2 wafers was evaluated using insulin, lysozyme, and fibrinogen. For all tested proteins, the polymer monolayers showed significant reduction (up to 98%) in nonspecific protein adsorption compared to the unmodified Si/SiO2 wafers. In addition, cell adhesion as probed using 3T3 fibroblasts was significantly reduced on the polymer-coated glass substrates in comparison to unmodified glass substrates.