Abstract: In order to optimize ultrasound-assisted extraction technology for the extraction of glycoprotein extraction from jellyfish (Rhopilema esculentum) oral-arms, on the basis of single factor experiments, the effects of operating conditions, such as ultrasonic time, ultrasonic power and extraction time on the yield of glycoprotein were analyzed by response surface methodology. The optimized conditions of ultrasound-assisted extraction were as follows: ultrasonic treatment time was 15min, ultrasonic power was 300W, and extraction time was 60min. Under the above-mentioned conditions, the actual yield of target glycoprotein was 9.14%, which is well matched with the predicted yield. Among three factors, ultrasonic treatment time and ultrasonic power had significant effects on the yield of glycoprotein, while extraction time had no remarkable effect. Moreover, there are no interaction among three factors.