Objective To study the matrix effects （MEs） and the compensation measures of 15 quinolones （QNs） determination in animal derived food by high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） .Methods Fish， pork and chicken as typical substrates were tested by post-extraction spiking method and dynamic multiple reaction monitoring to evaluate matrix effects.Results More than 60% of the quinolones suffered moderate and strong matrix effects in the three samples. Enrofloxacin， pefloxacin and dalfloxacin had strongly matrix enhancement effect， and fleroxacin was strongly inhibited. Pretreatment methods， matrix species， compound species and mass concentration were the main factors affecting the matrix effect of quinolones.Conclusion In the process of daily monitoring which the pretreatment method specified in the test standard cannot be changed casually， matrix matching standard curve， isotope internal standard， diluted sample and improving chromatography resolution combined with dynamic multi reaction monitoring could effectively compensate the matrix effect of quinolones and improve the reliability and accuracy of the detection results.