A HPLC method was established for the determination of phenytoin sodium. An Agilent XDB-C18 column was used, with methanol-water (60:40) as the mobile phase, and the detection wavelength was 220 nm. The calibration curve was linear in the concentration range of 1.00-64.00 μg/mL. The average recovery was 98.5%, with RSD of 0.38%. The method was simple, sensitive, and accurate, and could be used for the determination of phenytoin sodium.