A selective, sensitive and rapid hydrophilic interaction liquid chromatography with electrospray ionization tandem mass spectrometry was developed for the determination of donepezil in human plasma. Donepezil was twice extracted from human plasma using methyl tert-butyl ether at basic pH. The analytes were separated on an Atlantis HILIC Silica column with the mobile phase of acetonitrile: ammonium formate (50 mM, pH 4.0) (85: 15, v/v) and detected by tandem mass spectrometry in the selective reaction monitoring mode. The calibration curve was linear (r = 0.9994) over the concentration range of 0.10-50.0 ng/mL and the lower limit of quantification was 0.1 ng/mL using $200{mu}L$ plasma sample. The coefficient of variation and relative error for intra- and inter-assay at four QC levels were 2.7 to 10.5% and -10.0 to 0.0%, respectively. There was no matrix effect for donepezil and cisapride. The present method was successfully applied to the pharmacokinetic study of donepezil after oral dose of donepezil hydrochloride (10 mg tablet) to male healthy volunteers.