A novel derivative beta-cyclodextrin (beta-CD) bonded silica gel (beta-CD/SiO2) was prepared via carbodiimide activation and used as a chiral stationary phase (CSP). The beta-CD/SiO2 CSP was characterized by X-ray photoelectron spectroscopy and FTIR spectroscopy to prove the successful immobilization of beta-CD onto the surface of the silica gel. The thermal behavior of the CSP was studied by differential scanning calorimetry and then used for the chiral separation of racemic naproxen using HPLC. Several factors affecting the separation efficiency of naproxen enantiomers were investigated systematically. The following parameters were selected: methanol-0.01 M phosphate buffer solution (85 + 15, v/v, pH 3.5) was the mobile phase, the flow rate was 1.0 mL/min, and the column temperature was 35 degrees C. Under optimal conditions, the racemic naproxen was efficiently separated with a resolution factor (R(S)) of 1.70 and a separation factor (alpha) of 1.25. This method was successfully used for the enantiomeric separation and purity assessment of naproxen in commercial naproxen sustained release tablets.