Abstract: A simple method for the simultaneous quantification of 21 perfluoroalkyl acids in milk has been developed using solid-phase extraction (SPE) with anion-exchange resin and silica gel as the mixed packing material, combined with the liquid chromatography-mass spectrometry (LC-MS/MS) technique. A large amount of protein was precipitated by adding acetonitrile to the milk sample, and the extract solution was purified through the elution in a self-made solid phase extraction column using 1.5 mL of 80% acetonitrile water solution. The purified solution was analyzed using LC-MS under the following conditions: an XDB-C18 column with gradient elution using acetonitrile-5 mmol of aqueous ammonium acetate as the mobile phase, electrospray negative ionization mode ionization (ESI), the mass scan mode was multiple reaction monitoring (MRM) mode detection. The limits of detection (LOD) of perfluoroalkyl acids (PFAAs) were 0.01~0.20 ng/mL and the limits of quantification (LOQ) were 0.03~0.67 ng/mL. The linearity (R²>0.999) and reproducibility of the method were good, and the recoveries ranged from 66% to 125%. Thirteen common commercially available milk were analyzed for perfluoroalkyl acids, and seven perfluoroalkyl acids were mainly detected with milk mass concentrations ranging from 2.43 to 12.00 ng/mL.