Objective To establish an ultra-fast liquid chromatography (UFLC) method for detecting the substances in different preparations of nimesulide. Methods Ultra-fast liquid chromatography instruments Shimadzu and Syncronis C₁₈ column (100 mm×2.1 mm×1.7 μm) were used. The mobile phase was a mixture solvent of methanol-acetonitrile-0.1% solution of orthophosphoric acid (adjusted to pH 6.5 with ammonia)(45:15:40). The flowing rate was 0.3 mL/min,and the detection wavelength was 230 nm. The system suitability solutions of European Pharmacopoeia and Chinese Pharmacopoeia, the damaging samples and the accessories of different preparations of different manufacturers were used to investigate the method applicability. Results The method had high resolution, strong specificity and can efficiently and quickly detect the related substances in nimesulide preparations.Various degradation products of damaging tests and the accessories of different preparations from different manufacturers had no effect on the determination results. Conclusion The method is efficient, fast, widely applicable and can be used for detecting the substances in different preparations of nimesulide by different manufacturers.