Abstract: An ultra high-pressure liquid chromatography coupled electrospray ionization triple-quadruple tandem mass spectrometry (UPLC-ESI MS/MS) was used for the simultaneous determination of furazolidone, nitrofarazone, nitrofarantoin, furaltadone and chloramphenicol in fisheries water. The drugs were extracted and cleaned up by Oasis HLB solid phase extraction cartridge. The extract was evaporated to dryness under nitrogen and reconstituted in solution with V（acetonitrile）∶ V（water）=1∶1. The 5 drugs were separated and detected by ZORBAX SB-C18 using 0.1% formic acid (A) and acetonitrile (B) as mobile phase. The target compounds were confirmed and quantified by MS/MS under multiple reactions monitoring (MRM) mode with external standard method. Under the optimal condition, the calibration curves of 5 drugs show good linearity with the correlation coefficients rather than 0.997 in the range of 0.5 μg/L or 1—40 μg/L, the limits of detection(LODs) range from 0.5—1.0 μg/L (S/N=3), the average recoveries of 5 drugs are in the range of 90.3％—104.2％， and the relative standard deviations(RSDs) are 5.4％—10.0％.