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The leaves of Jerusalem artichoke (Helianthus tuberosus L.) have been reported to possess anticancer activities.Sesquiterpene lactones (SLs) are the dominant active constituents of Jerusalem artichoke leaves.Consequently, simultaneous determination of SLs could be a better strategy for the comprehensive quality evaluation of Jerusalem artichoke.An ultra performance liquid chromatography (UPLC) coupled to photodiode-array detection and quadrupole time-of-flight mass spectrometry (Q-TOF) method was developed for the rapid qualitative and quantitative analyses of eleven SLs in Jerusalem artichoke leaves in 15 min.The optimal chromatographic conditions were achieved on a ZORBAX Eclispse Plus C18 column (3.0× 150mm, 1.8 micron) with linear gradient elution of methanol and water.Quantitative analysis was carried out under selective ion monitoring (SIM) mode.