A mathematical model based on Fick's first law was established to describe ultrasound-assisted extraction of capsaicin from red peppers. By considering the mechanism of ultrasound-assisted extraction and the experimental data, the effects of parameters (ultrasound power, extraction temperature and extraction time, solvent/sample ratio, ethanol volume fraction) on yield of capsaicin would be analyzed in detail. The model was very convenient for obtaining optimal parameters in the ultrasound-assisted extraction of capsaicin. The calculation result by the model was agreed with the experimental data very well, indicating that the mathematical model could provide valuable guidance for the ultrasound-assisted extraction of capsaicin from red peppers.