People depend on food to survive, so we must put the quality and safety of food first.However, it is very difficult to identify the unknown food additives for their kinds are a large number, their concentrations are low and the background information about them is little.In this paper, a method for the rapid and accurate screening target and/or non-target additives in food was developed by the combination of sequential extraction and liquid chromatography/gas chromatography-mass spectrometry.The sequential extraction using hexane and ethyl acetic respectively, and then the extractions were analyzed by GC-MS/Scan.The doubtful peaks were identified by NIST library and validated by GC-MS/SIM using standards.The residual samples after extraction were analyzed by LC-HRQ/TOF based on a self-established library which containing 135 kinds of food additives.After using this method to screen unknown additives in red wine samples, some food additives including benzoic acid and sorbic acid were identified.Comparison the sensitivity of HPLC-MS/MS and HPLC-Q/TOF demonstrated that the latter was only 10 times less than the former.This work is helpful to detect unknown or banned additives in food, and to improve the peoples health.