A qualitative and quantitative analysis method has been established forsimultaneous determination of six kinds of sweeteners (sodium cyclamate, saccharinsodium, acesulfame K, trichlorosucrose, aspartame and neotame) and five kinds of preservatives (natamycin, sodium benzoate, potassium sorbate, sodium dehydroacetate and sodium diacetate) in food by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The sample did not need to derive and purify, directing ultrasound extraction with methanol and water, separated on a Shim-pack-ODS Ⅲ column (75 L ×2.0 mm, 1.6 μm), used acetic acid ammonium (10 mmol/L)-methanol as the mobile phase for gradient elution. The ionization efficiencies of target compounds in mass spectrometry were analyzed for different mobile phases at same time. The results indicated that the six kinds of sweeteners and five kinds of preservatives showed a good linear relationship (R²＞0.996) with the peak area in the range of concentration measured. The average recovery of standard addition was 73.4%~96.8%, and the relative standard deviation (RSD) was 1.6%~7.8%.