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<b>Objective:</b> This study focused on improving comprehensive utilization rate of ziziphi spinosae semen resources. <b>Methods:</b> With the ultrasonic power, ultrasonic time, solid-liquid ratio, ethanol volume fraction and ultrasonic temperature as the influencing factors, and the extraction rate of isovitexin-glucopyranoside in ziziphi spinosae semen as the index, the extraction process parameters of isovitexin-glucopyranoside were optimized by response surface methodology. <b>Results:</b> The optimal extraction conditions of isovitexin-glucopyranoside were ultrasonic power 405 W, ultrasonic time 60 min, solid-liquid ratio 1∶16 （g/mL） and ethanol volume fraction 75%. Under the control of these conditions, the extraction rate of isovitexin-glucopyranoside was 0.705%, which was close to the predicted value （0.719%）, indicating that the predicted value of the extraction rate of isovitexin-glucopyranoside fit well with the actual situation. <b>Conclusion:</b> The ultrasonic assisted extraction of isovitexin-glucopyranoside is stable and reliable with high extraction rate.