Abstract: Hydrolytic technics of collagen from squid skin by protease was studied. Based on the content of hydroxyproline of five kinds of enzymic hydrolysates, trypsin and papain were chosed to apply in the experiment. By L16(45) orthogonal experiment design, the optimum processing conditions of extraction by trypsin and papain were determined. Results of extracting collagen show that the optimal conditions of trypsin and papain were temperature 55℃, enzyme dosage 1 200 Ug-1, concentration of substrate 1:20, pH 8.0, time 4 h, and temperature 50℃, enzyme dosage 3 200 Ug-1, concentration of substrate 1:20, pH 6.0, time 6 h, respectively. The content of collagen was 11.08% and 11.36%, respectively. Extraction yield of collagen was 95.16% and 97.56%, respectively.