This short communication introduced a simple and sensitive LC-MS/MS method for therapeutic drug monitoring of digoxin in children with the lower limit of quantitation of 0.2 ng/mL based on 30 mu L of plasma. The plasma sample was pretreated by one-step protein precipitation. Then the chromatographic separation was performed on a short C-18 column with a total run time of 2.4 min. The detection was achieved through multiple reaction monitoring using positive ionization mode on a triple quadrupole mass spectrometer. The linear range of digoxin in human plasma was among 0.2-6.4 ng/mL. The intra-day and inter-day accuracies of digoxin ranged from -6.0 % to 10.1 % and imprecisions were less than 8.8 %. The extraction recovery rate of digoxin in plasma samples was above 90 %. Matrix factor normalized by internal standard was within acceptance criteria. This method was fully verified and applied to determine the plasma digoxin concentrations of 43 pediatric patients. It is approved appropriate and practical for the therapeutic drug monitoring of digoxin in routine clinical laboratory practice, especially for children.