Objective: To establish the determination of Shexianbaixin Pill. Methods: HPLC was applied to determine cinobufagin and resibufogenin. The determination was carried out using an ODS column with a solvent system: acetonitrile 0.5KH 2PO 4. The flow rate was 1.0mL?min -1 , detection wavelength was at 296nm and the column temperature was at 35℃. Results: The linear ranges of cinobufagin and resibufogenin were 0.148?g～0.746?g and 0.116?g～0.580?g, respectively. The average recoveries of cinobufagin and resibufogenin were 100.90%( RSD =1.004%, n =5), and 100.64%( RSD =1.006%, n =5), respectively. Conclusion: This method is simple, accurate with strong specificity and can be used to control the quality of Shexiangbaoxin Pill.