A simple and sensitive method of gas chromatography–mass spectrometry for quantification of β-elemene in human plasma was developed and validated. An n -hexane-based liquid–liquid extraction assisted by saturated sodium chloride solution was used for sample preparation. Naphthalene was chosen as the internal standard. The calibration curve ( r 2 = 0.9997) of β-elemene was established at the range of 0.0655–40.00 μg mL −1 and the lower limit of quantification (LLOQ) was 0.0655 μg mL −1 using 200 μL of plasma, respectively. The accuracy was in a range of 87.1–101.7 %, and intra- and inter-day precisions (RSD %) at three QC levels were all less than 10 %. The LLOQ of 0.0665 μg mL −1 is sensitive enough to perform pharmacokinetic studies after β-elemene administration.