A method based on matrix solid-phase dispersion(MSPD) and high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) using isotope dilution technique was developed for the simultaneous determination of four β2-agonists，e.g.clenbuterol，ractopamine，salbutamol and terbutaline in sausage sample.The sausage samples were graphitized with C18 and eluted with methanol.After enzymolysis，the extracts was purified with solid phase extraction MCX cartridges.The separation of analytes was performed by HPLC，and the identification of target compounds was achieved under multiple-reaction monitoring mode with electrospray ionization in positive mode.Four β2-agonists were quantified by the internal standard method.The calibration curves showed good linearities for four β2-agonists in the range of 0.2-20.0 μg/L with correlation coefficients (r2) more than 0.990.The limits of detection were 0.10 μg/kg for salbutamol and clenbuterol,and 0.15 μg/kg for terbutaline and ractopamine.The spiked recoveries ranged from 80% to 109% with relative standard deviations less than 10%.The method showed the advantages of simplicity，sensitivity and less consumption of sample and organic solvents，and could meet the requirements for the determination of clenbuterol，ractopamine，salbutamol and terbutaline in sausage sample.