Abstract: Collagen performs a triple-helix structure that is formed by three α chains through right-hand spiral of hydrogen bonds between peptide chains. It has high stability and large molecular weight, accounting for about one-third of the total protein in animals. Collagen can provide high mechanical strength to bone, skin, tendon, blood vessels, and other tissues to support organs and maintain normal physiological functions of the body. It has a great influence on the normal functions of cells, tissues, and organs, and can repair damaged parts. Collagen has good application prospects because of its low sensitivity and biocompatibility, and can be applied to food, medicine, cosmetics, and food packaging. Chicken skin consists of about 10% of protein, 85% of which is collagen. Therefore, it can be used as a high-quality protein source to be applied in food industry and increase its added value. In this study, the process of extracting collagen from chicken skin by ultrasound-assisted enzymatic extraction was studied. Taking solid-liquid ratio, pepsin dosage, ultrasonic output power and ultrasonic treatment time as experimental factors, the technology of ultrasonic assisted enzymatic extraction of collagen was explored, and the prediction model was established to optimize the extraction process. Firstly, the influence of 4 factors on collagen extraction and their optimal range were determined by single-factor experiments. Then, the response surface was optimized. The results showed that ultrasonic-assisted enzymatic preparation significantly improved the extraction rate of collagen, and ultrasonic power and ultrasonic time had significant (P<0.05) effect on extrac-tion rate. In addition, the optimal extraction condition was obtained based on regression equation and prediction model: the solid-liquid ratio of 1 : 73 g/ mL, enzyme dosage of 1.58%, ultrasonic power of 260 W, and ultrasonic time of 26 min (2 s On-2 s Off). Among the four independent variables, ultrasonic treatment time played the most important role on extraction rate, followed by ultrasonic power, solid-liquid ratio, and enzyme content. The extraction rate reached 83.42% ± 0.65% under the optimal conditions, which was consistent with the predicted value. Therefore, it is demonstrated that the ultrasound-assisted enzymatic extraction could significantly improve the extraction efficiency of collagen compared with traditional acid extraction methods, and it can be used in industrialized preparation of chicken skin collagen. This paper provides theoretical support for the extraction and utilization of collagen in animals, which is more conducive to the application and development of collagen.