A high-performance liquid chromatographic(HPLC) method was developed for the determination of relative substances in diclofenac sodium gel.The separation of analyte was performed on a Waters XBridge column(5 μm,150 mm×4.6 mm) at a flow rate of 1.0 mL/min and an injection volume of 5 μL,by a gradient elution using pH 2.0 trifluoroacetic acid - methanol(80∶20) as mobile phase A and acetonitrile - methanol(80∶20) as mobile phase B.The photo-diode array detector(PDA) was set at 254 nm.The column temperature was 30 ℃.Under the above chromatographic conditions, the calibration curves were linear in the range of 1.0-40.0 mg/L with correlation coefficients more than 0.99.The recoveries for all the specified impurities ranged from 97% to 104% with RSDs not more than 3.8%.The proposed method could be applied in the determination of relative substances in diclofenac sodium gel containing alcohols excipients with the advantages of simplicity,rapidity,accuracy,good selectivity and high sensitivity.