Abstract: A method for simultaneous determination of residues of 6 diuretics, including bumetanide, furosemide, chlorathiazide, hydrochlorothiazide, antisterone and dyrenium in surface water around pharmaceutical factory by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with online solid phase extraction was proposed. An aliquot (20 mL) of treated surface water sample around the pharmaceutical factory was taken and placed into the automatic sampling tray of the online solid phase extraction instrument, and WATERS Oasis HLB solid phase extraction column was used for extraction, purification and enrichment. The obtained solution was automatically transferred into the chromatographic system, Shim-pack CLC-ODS C₁₈ column was used as the stationary phase, and the mixed solutions composed of 0.1% (volume fraction) formic acid solution and methanol at different volume ratios were used as the mobile phase for gradient elution. The 6 separated targets were scanned by positive ion mode of electrospray ion source, detected by multiple reaction monitoring mode, and quantified by external standard method. It was shown that the linear ranges of the standard curves for 6 targets were 0.005-10.0 mg·L^-1, with detection limits (3S/N) in the range of 0.035 1-0.147 μg·L^-1. Test for recovery was made on the actual sample at 3 concentration levels according to the standard addition method, giving results in the range of 83.3%-104%, and RSDs (n=6) of the determined values were less than 5.0%.