Objective To optimize the sample pretreatment process by using HLB-P/HMR-Lipid SPE purification column. In combination with ultra-high performance liquid chromatoplc-tandem mass spectrometry， a method for simultaneous detection of 19 fluorinated alkyl compounds in liquid milk was established.Methods The sample was extracted by means of acetonitrile dissolving precipitated protein vortex， and the commercial double-layer solid phase extraction column HLB-P/HMR-Lipid SPE was used to purify the lipid. Then the methanol-water （8∶2， v/v） was redissolved after nitrogen blowing， and the mobile phase gradient elution was performed by using methanol and 2mmol/L ammonium formate solution. The targets were separated by ACQUITY Premier BEH C18 column （100 mm×2.1 mm，1.7 μm）， detected by electrospray ion source and negative ion multi-reaction monitoring mode， and quantified by internal standard method.Results The linear relationships of 19 fluorinated alkyl compounds were good in the range of 0.1-50 μg/L， and the correlation coefficient r was greater than 0.995. The limit of detection was 0.003 7-0.009 5 μg/kg and the limit of quantification was 0.012 4-0.031 7 μg/kg. The recoveries of low concentrations（0.1 μg/kg）， medium concentrations（1 μg/kg） and high concentrations（8 μg/kg）in liquid milk ranged from 73.8% to 113.1%， the relative standard deviations were less than 10% （n=6）.Conclusion The method is accurate， reliable， sensitive， reproducible and suitable for the detection of fluorinated alkyl compounds in liquid milk.