A mathematical model based on Fick's first law was established to describe the process of ultrasonic-assisted extraction of arctigenin from acid hydrolyzed FructusArctii. Acid hydrolization with hydrochloric acid promotes the conversion of arctiin to arctigenin in the arctiin-rich active pharmaceutical ingredient, and the hydrolyzed products were further examined to investigate the process setup. By considering the mechanism of the extraction process and experimental data, the effects of parameters including solvent to solid ratio, particle size of hydrolyzed samples, ethanol volume fraction, ultrasound power, extraction temperature and extraction time on concentration of arctigenin were analyzed in detail. The model was suitable for simulating the process of ultrasonic-assisted extraction of arctigenin. The simulation results of the model agree well with experimental data with the deviation below 13%, indicating that the mathematical model can provide valuable guidance for the extraction of arctigenin from acid hydrolyzed FructusArctii.