Abstract: The present study discussed about the ultrasound-assisted protease hydrolysis from sepia.The enzymatic hydrolysis degree was investigated to screen the optimum protease,while enzymatic hydrolysis conditions were optimized by single factor test and L₁₆(4⁵) orthogonal test.The experimental results showed that acid protease was the optimum protease,whose optimum hydrolysis condition was optimized as follows:temperature 50℃,reaction time 2 h,pepsin amount 3.0%,pH 3.5 and solid liquid ratio 1:15.Under the optimized conditions,the degree of hydrolysis of sepia was 11.45%.The content of oxidation product PTCA of hydrolyzed melanin was 17.621 μg/mg and the total antioxidant capacity of hydrolyzed melanin was 18.9 U/g,while the retention rate was 99%.