Propofol (2,6-diisopropylphenol) is widely used in total intravenous anesthesia. An unknown drug concentration in blood always leads to some side effects in patients with propofol injection. However, the drug concentration in the blood is hard to be continuously measured since invasive sampling causes a loss of blood at each measurement. Here, we introduced a virtual surface acoustic wave sensor array (VSAWSA) to non-invasively detect the propofol concentration in blood through exhaled gases. Calibration was conducted by a parallel test using gas chromatography and mass spectrometry (GC-MS) with solid-phase micro-extraction (SPME) for preconcentration. The limit of detection of VSAWSA reached 0.15 nmol/L for propofol. Six cases of clinical trials was conducted to compare the exhaled propofol concentrations to the plasma concentrations controlled by target-controlled infusion (TCI). The calibration by GC-MS ensured the feasibility, reliability, and accuracy of the VSAWSA (R = 0.9904, p <0.001). The clinical monitoring data by VSAWSA showed an excellent consistency with TCI.