A new method and mass spectral database for screening pesticide residues in fruits and vegetables by liquid chromatography-high resolution benchtop/orbitrap mass spectrometry（HRMS） with on-line cleanup were developed.The samples were extracted with acetonitrile containing 0.1% acetic acid,then purified and collected with a Cyclone-P column.The analytes were separated on a C18 column with acetonitrile-0.5 mmol/L ammonium acetate containing 0.1% acetic acid as mobile phase by gradient elution.212 pesticides residues were analyzed by high-resolution mass spectrometry Q-Orbitrap in full scan/ddMS2 mode under switching positive and negative mode.The calibration curves were linear in the range of 0.5-50 μg/L with correlation coefficients more than 0.998.The limits of quantitation（LOQs） reached to 5 μg/kg.The average recoveries of the analytes at a spiked level of 10 μg/kg were in the range of 58.3%-129.4%,with their relative standard deviations of 2.8%-16.0%.The method could be used for the rapid screening of 212 compounds in fruits and vegetables by means of accurate mass of quasi-molecular ion,retention time,isotope ratio and qualitative fragments without any reference standards.