This work describes an optimized supercritical fluid extraction (SFE) process of osthole and imperatorin from the fruits of Cnidium monnieri (L.) Cusson. Response surface methodology (RSM) was employed to evaluate the effects of independent variables on the yields of osthole and imperatorin. The independent variables were extraction pressure (100 to 300bar), temperature (50 to 70 degrees C), and ethanol flow rate (0 to 0.4mL/min). Results indicated that the data could be well fitted to two second-order polynomial models in the selected experimental domain. The effects of independent variables of pressure, temperature, ethanol rate flow, as well as the interactions between pressure and ethanol flow rate, and between temperature and ethanol flow rate on the extraction yield were significant for osthole or imperatorin extraction (p<0.05). The models predicted that the optimized conditions were 243bar, 64 degrees C, ethanol flow rate of 0.28mL/min, giving maximum yields of 1.29% and 0.53% for osthole and imperatorin, respectively, that were in good agreement with the experimental values. The extraction yields obtained with the optimized SFE and Soxhlet extraction were compared.