Herein we reported the PEGylated hollow mesoporous silica (HMS-PEG) nanoparticles as drug vehicles for drug delivery. Hollow mesoporous silica (HMS) nanoparticles with the diameter of ca. 100 nm were synthesized using the colloidal carbon spheres as templates, and HMS-PEG nanoparticles were successfully prepared by covalently grafting poly(oxyethylene)bis(amine) on amino-group modified HMS nanoparticles with p-phenylene diisothiocyanate (DITC) as a cross linker. HMS-PEG nanoparticles exhibited much better dispersity and stability in aqueous solution than HMS nanoparticles. In vitro cytotoxicity and cell uptake of HMS-PEG nanoparticles to Hela and NIH3T3 cells were evaluated. HMS-PEG nanoparticles have little in vitro cytotoxicity up to a concentration of 150 μg/ml, and the uptake amount of HMS-PEG nanoparticles is approximately two times than that of HMS nanoparticles in Hela and NIH3T3 cells. Doxorubicin hydrochloride (DOX), an anticancer drug, was loaded into HMS-PEG nanoparticles, and the DOX-loaded HMS-PEG nanoparticles had a sustained release property. Furthermore, the DOX-loaded HMS-PEG nanoparticles exhibited higher cytotoxicity than the DOX-loaded HMS nanoparticles against Hela and NIH3T3 cells. Therefore, the PEGylation of HMS nanoparticles is a promising strategy toward their potential application as drug delivery vehicles.