ZnO nanoparticles have been identified as a new generation of biofriendly cell labeling agents since they are nontoxic, less expensive, and chemically stable in air. However, ZnO nanoparticles show poor water stability due to high equilibrium concentration of Zn species in water in a wide pH range. In this work, a one-pot polyol hydrolysis method was developed for synthesizing water-stable ZnO nanoparticles with blue emission. The as-synthesized ZnO nanoparticles were hydrophilic and stable in water, even at basic or acidic aqueous conditions. The PL properties of the ZnO nanoparticles stored at various pH values (i.e., 4.5-11) could be preserved for at least 3 days. The good water stability of the ZnO nanoparticles was offered by the surface attachment of an ester compound, which was formed as a result of the reaction between the stearic acid and triethylene glycol (TREG). This method provides a new approach to synthesize water-stable ZnO nanoparticles. The resultant ZnO nanoparticles demonstrated promising applications in cell labeling.