Abstract: OBJECTIVE To optimize extraction method of total alkaloids from Stephania tetrandra by enzyme with ultrasonic technology. METHODS Orthogonal experiment and response surface methodology was employed to optimize the technology conditions for extracting total alkaloids from Stephania tetrandra on the basis of single factor test. Taking total alkaloids extraction yield as evaluation index, optimize extraction conditions of total alkaloids from Stephania tetrandrs by enzyme with ultrasonic technology. RESULTS The optimum condition were as follows:compound enzyme was 2%, enzyme solution pH was 4.5, enzymolysis time was 1 h, enzyme solution temperature was 50℃, use 17 times of 74% ethanol ultrasound 30 min for 2 times, ultrasonic power was 165 W, ultrasonic temperature was 40℃. Under these conditions, the extraction rate of total alkaloids from Stephania tetrandra was 3.92%. CONCLUSION Ultrasonic assisted enzymatic extraction total alkaloid from Stephania tetrandra is an effective extraction method. The extraction technology is simply, stable, feasible and suitable for large industrial production.