To establish a determination method for the potential genotoxic impurities (Me methanesulfonate and Et methanesulfonate) in nafamostatmesylate. GC-MS was conducted, and the potential genotoxic impurities were extracted by dichloromethane with iso-Pr methanesulfonate as internal standard The column was HP-5 capillary column with programmed temperature, the inlet temperature was 240°C, the column flow was 1.5 mL/min and the carrier gas was high purity helium, the detector was a mass spectrometer detector, the ion source temperature was 230°C, the interface temperature was 260°C, the delay time of solvent was 2.5 min, the detector voltage was respect to the tuning results, the scanning (detection) method was selective ion monitoring (SIM), the electron energy was 70 eV, and the injection volume was 1.0 μL. Me mesylate and Et mesylate could be separated completely with good linear relationship between 0.01-0.4 μg/mL, the average recoveries were 90.2% and 97.0%, the limits of detection were 5 ng/mL and 3 ng/mL, the limits of quantitation were 14.8 ng/mL and 7.5 ng/mL. The method is simple, sensitive and accurate, and can be used for the potential genotoxic impurities in nafamostatmesylate.