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) 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,1.7μm), 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 0.1-50μg/L, and the correlation coefficient r was greater than 0.99. The limit of detection was 0.0037~0.0095μg/kg and the limit of quantification was 0.0124~0.0317μg/kg. The recoveries of low concentrations（0.1μg/kg）, medium concentrations（1μg/kg） and high concentrations（8μg/kg）in liquid milk ranged from 73.8% to 113.1%, and 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.