To overcome the disadvantages of protein denaturation and nonspecific adsorption on poly(styrene-divinylbenzene) (PS) matrix as chromatographic supports, gigaporous PS microspheres, which we prepared in a previous study, were chemically modified with poly(vinyl alcohol) (PVA) through two-step reaction. The microspheres were chloroacetylated through Friedel-Crafts acetylation with chloroacetyl chloride and modified with hydrophilic PVA through Williamson reaction afterward. The modified microspheres were characterized by Fourier transform infrared (FTIR) spectra, X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), mercury porosimetry measurements (MPM), BET nitrogen adsorption measurements, laser scanning confocal microscope (LSCM), and protein adsorption experiments. Results showed that PS microspheres were successfully coated with PVA, while the gigaporous structure could be maintained. Consequently, the hydrophilicity and biocompatibility of modified microspheres was greatly improved and nonspecific adsorption of proteins was significantly decreased. The coatings contained only stable chemical bonds (e.g., C-C, C-O-C) and easily derived hydroxyl moieties. The large pores of gigaporous PS microspheres also facilitated the modification by PVA. After further derivation, the coated gigaporous base supports could apply in various modes of chromatography and have great potentials in high-speed protein chromatography. (c) 2008 Wiley Periodicals, Inc.