An ultrahigh performance liquid chromatography-quadrupole-time of flight-mass spectrometric(UPLC-Q-TOF-MS) method was established for the qualitative analysis of impurities in orlistat hydrogenation solution.The isocratic elution was performed on a Thermo Hypersil gold aq C18 column(2.1 mm×150 mm，1.9 μm) with 0.1% acetic acid aqueous solution-0.1% acetic acid acetonitrile(25∶75) as mobile phase.The MS was operated with an electrospray ionization(ESI) source in positive ion mode within a sanning range of m/z 50-600.The nebulizing temperature was set at 300 ℃ and the dry gas flow was 10 L/min.The exact mass and fragmentions of 16 impurities were acquired by Q-TOF-MS after separation by UPLC.Structures of the impurities were analyzed and their originations were deduced.More than 0.1% impurities in orlistat hydrogenation solution were generated mainly in the process of fermentation,which need be purified in the next procedure.The results obtained provided a reference for the optimization of manufacturing process and quality control of orlistat.