Objective To establish a method for detection of vitamin A and vitamin E in infant milk powder with high performance liquid chromatography (HPLC) by solid phase extraction. Methods After saponification,the saponified solution was purified by the SPE cartridge, the eluent was collected and applied a nitrogen evaporation. After redissolution, the analytes were detected by HPLC, using methanol as mobile phase, separated by Zorbax C₁₈ column (4.6 mm×150 mm, 5 μm) and calculate by the external standard method. Results Vitamin A had a good linear relationship within 0.5-5.0 mg/L and 5.0-50 mg/L for vitamin E, the correlation coefficients of the standard curve of 0.999. The recoveries at three spiked levels were from 86.0%-104.6% and 89.0%-104.0%, and the relative standard deviations (RSD) were less than 3.0%. The limit of detection (LOD) were 1.0 and 10 μg/100 g. Conclusion This method could be applied to the detection of vitamin A and vitamin E in infant milk powder at the same time, and it was simple, fast and accurate.