Objective To establish a rapid non-targeted pesticide residue screening platform involving more than 1200 pesticides residues and their degradation products by using gas chromatography tandem mass spectrometry/mass-spectrometry and ultra performance liquid chromatography-Q-Orbitrap technology for unknown pesticide residue in botanical food, on the basis of original screening platform. Methods The principal and criterion of pesticides screening platform were established, and the platform was evaluated through twice proficient tests from Europe Union Reference Lab. Results The platform successfully completed the tests based on comprehensive database and blank matrix in 24 h with 90% screening rate and without false positive. Conclusion The platform achieved rapid screening of non-targeted pesticide residue without reference of standard materials by using the properties of high selectivity of triple quadrupole and high-resolution mass spectrometer combined with comprehensive pesticides database and advanced compound screening software.