A high-throughput qualitative screening and quantita-tive method of ultra-high performance liquid chromatography combined with orbitrap mass spectrometry（UPLC-Orbitrap-MS） was developed to determine 73 kinds of chemicals illegally added in the healthy foods. The samples were extracted with methanol using ultrasonic extraction. The separation was eluted by gradient on a Waters Acquity UPLC HSS T3 column (100 mm×2.1 mm, 1.8 μm), with a mobile phase consisting of water (0.1% formic acid) and acetonitrile in both positive and negative mode. The data were acquired via full-scan data-dependent MS/MS (full scan-ddMS²). The qualitative analyses of the compounds were performed through the database established by Trace Finder software, and the quantitative detection were undertaken through the area of precursor ions. The results showed that each target had good linearity in its own concentration range, and the correlation coefficients were higher than 0.99. The limits of determination (LODs) were between 2～20 μg/kg, and the limits of quantification (LOQs) were between 6～60 μg/kg. The recoveries of the proposed method were in range of 72.2%～117.5% at spiked levels of 100, 200, and 1 000 μg/kg with deviations (RSDs) between 2.3%～6.8%. It could be concluded that the high-throughput, qualitative and quantitative method reported in this study was useful for the determination of illicit drugs in functional foods.