The invention discloses a method for determining the concentration of lacosamide in blood plasma by liquid chromatography-mass spectrometry, which adopts a liquid chromatography-mass spectrometry system for determination, and comprises the following steps: taking a sample to be detected, adding a certain amount of mixed organic solvent for extraction and pretreatment, separating by a chromatographic column, and detecting by a mass spectrometry detector. The method disclosed by the invention is rapid, accurate, high in sensitivity and simple and convenient to operate, and provides a basis for determining the blood concentration of lacosamide; and according to the method, the linear range of the plasma standard curve is 100-15000 ng/mL, the intra-batch precision RSD and the inter-batch precision RSD are both smaller than +/-15%, and the method is suitable for measuring the concentration of lacosamide in plasma.