OBJECTIVE To optimize the processing technology of wine steamed Cnidii Fructus. METHODS The content of xanthotoxol, xanthotoxin, bergapten, isobergapten, imperatorin and osthole was used as the evaluation index. The response surface methodology combined with entropy weight method was used to investigate the adding amount of rice wine, the soaking time and the steaming time with aim to find the best processing technology. RESULTS The best processing technology for Cnidii Fructus with wine steaming was: adding 30 g of rice wine 4 mL for infiltrating 18.5 h, and steaming for 10 h. CONCLUSION The optimized wine steaming process is stable and feasible. The establishment of an HPLC analytical method for the determination of 6 components in wine steamed Cnidii Fructus is accurate and reliable, which can be used for the quality control of wine steamed Cnidii Fructus decoction pieces.