Porous nanosilica (PNS) has been attracting much attention in fabrication of nanocarriers for a drug delivery system (DDS). However, the unmodified PNS-based carriers exhibited a significant initial burst release of drug, which may limit their potential clinical application. In this study, PNS was surface conjugated with cyclodextrin (CD) which was functionalized with adamantylamine-polyethylene glycol (APEG) for 5-fluorouracil (5-FU) delivery, in which case CD was used due to its ability to form a stable inclusion complex with 5-FU and APEG. The conjugated PNS (PNSC@APEG) was successfully prepared with spherical shape and diameter around 50 nm, determined by transmission electron microscopy (TEM). In addition, 5-FU was efficiently trapped in PNSC@APEG particles, which were around 63.4%±3.8% and was slowly released up to 3 days in phosphate buffer saline (PBS). Furthermore, the cell proliferation kit I (MTT) assay data showed that PNSC@APEG was a biocompatible nanocarrier. These results indicated that PNSC@APEG nanoparticles have a great potential as novel carriers for anticancer drug delivery.