Abstract: Mechanical parameters and extraction parameters were studied by using the yields of chlorogenic acid and hyperoside as indicators, which afforded the optimal mechanically-assisted extraction condition for phenolic compounds from Senecio Scandens Buch.-Ham. by further employing response surface methodology. The results showed that the optimal mechanical parameters were as follows: milling ball filling degree 27.6%, milling speed 308 r/min and milling time 11.5 min, followed by single extraction in water for 10 min to give chlorogenic acid and hyperoside in ( 5.040 ± 0.042) mg/g and ( 0.485 ± 0.004) mg/g yield, respectively.Compared with heat reflux extraction and decoction, mechanically-assisted extraction was more efficient for rapid extraction of phenolic compounds at low extraction temperature without using organic solvent. Besides, the yield of hyperoside was increased substantially with obvious decrease of the residual pyrrolizidine in the extracts.