Donepezil HCl is a hydrochloride salt of a piperidine derivative acetylcholinesterase inhibitor and, it uses in treatment demantia of Alzheimer’s disease. In this study, a sensitive and rapid HPLC-UV method was developed and validated for determination of Donepezil HCl in API and tablet dosage forms. Chromatographic separation was performed using a Ace 5 C18 (5 ?m, 250 x 4.6 mm) by using isocratic phosphate buffer at pH:2.0 and acetonitrile (55:45, v/v) mobile phase was used at the rate of 1.2 mL/min. The column temperature was set at 30 ?C and the UV detection was recorded at 268 nm. The method was validated with respect to specificity, precision, accuracy, linearity, repeatability and reproducibility parameters in a concentration range of 25-125 µg/mL. The limit of detection (LOD) and limit of quantification (LOQ) were determined as 1.40 and4.20 µg/mL, respectively. The uncertainty budget of the measurement for Donepezil HCl was estiamted as 5.80 % at 95% confidence level (k = 2).