ZnO nanocrystals (NCs), potential candidates for photoluminescent applications, have attracted increasing attention recently because of their good biocompatibility, low cost, and convenient synthesis. However, their stability and fluorescent quenching, particularly in the aqueous phase, still hampers their use in biological applications. We report herein the synthesis of ZnO NCs modified by amphiphilic methoxy poly(ethylene glycol)-grafted poly(styrene-alt-maleic anhydride) (SMA-g-MPEG) copolymer based on the solgel method. We demonstrated a simple solution to address those challenges. Compared with unmodified ZnO NCs, SMA-g-MPEG modified ZnO NCs exhibited a significantly improvement in the stability and photoluminescent properties in the aqueous phase over current unmodified ones. This simple synthesis provides a novel platform for the preparation of ZnO NCs for biological applications. (c) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013