A high performance liquid method(HPLC) gradient elution method for determination of related substances in cefpodoxime proxetil for suspension was established. The chromatographic conditions are octadecyl silane bonded silica was used as filler(Kromasil C18， 150×4.6 mm， 5 μm), anhydrous formic acid-methanol-water(1∶400∶600) was used as mobile phase , andnhydrous formic acid- water- methanol (1∶50∶950) was used as mobile phase B, column temperature was 20℃； gradient elution method [0 min (95%A)→145 min (15%A)→155 min (95%A) was used at the flow rate of 0.6 mL/min and the detection wavelength was 254 nm. Results show that the method is proved to be feasible after the methodology verifying test. There was a good linear relationship when the Cefpodoxime concentration is in the range from 1.92-11.52 μg/mL . The linear equation is: Y(area of peak) = 70.565X(concentration) -5.8576. The test solution is stable within 10 h. The method is sensitive, accurate and specific and suitable for detecting the related substance in Cefpodoxime proxetil for Suspension.