Matrix effects are universal phenomena in analysis of liquid chromatography-mass spectrometry.By evaluating ‘Ion suppression’,matrix effects of diaveridine,sulfameter,ciprofloxacin,enrofloxacin,chlorotetracycline and tylosin in swine manure detected by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry(UPLC-ESI-MS/MS)were systematically investigated.The sample was extracted with McIlvaine-Na2EDTA buffer solution,purified and concentrated by a HLB Extraction Cartridge.The residue was dissolved by 0.1% formic acid-methanol(85∶15，by volume).The target compounds were separated on an SB C18 RRHD chromatographic column with 0.1% formic acid-methanol as mobile phase by gradient elution and detected in multiple reaction monitoring(MRM) mode via positive electrospray ionization(ESI+).The result showed that matrix enhancement effects existed in the detection of six antibiotics in swine manure.Furthermore,matrix-matched calibration curve and modified sample treatment could be used to compensate or eliminate the matrix effects in analysis of six antibiotics in swine manure.The study provided a reference for improving the accuracy and precision of the detection result.