The work aims to optimize the method of determining migration of bisphenol F and bisphenol S in food packaging plastics by HPLC-MS/MS. Under the optimized conditions of chromatography and mass spectrometry, the food simulants obtained from migration test were separated by C18 column, eluted by methanol-ammonia, monitored by multiple-reaction monitoring mode and quantified by external standard method. The linear relationship of bisphenol F and bisphenol S was good. The detection limits of water-based simulant were 4 μg/L and 0.2 μg/L, and quantitative limits were 10 μg/L and 0.5 μg/L, while the detection limits of oil-based were 20 μg/kg and 1 μg/kg and quantitative limits were 50 μg/kg and 2.5 μg/kg. The recovery rate was 89.2%~105.5% and RSD was 1.42%~6.18%. The method is accurate and sensitive, and suitable for the migration determination of bisphenol F and bisphenol S in food packaging plastics.