Abstract: For high-valued development and utilization of fish scale,an important fish-processing byproduct,after optimizing preparation technology through orthogonal experiments,fish scale collagen composite hemostatic sponge which possessed three-dimensional porous honeycomb structure was obtained by means of cross-linking reaction which combined type I fish scale collagen with chitosan.Then a series of systematic comparative studies about the hemostatic and antiallergic property and biocompatibility of the composite sponge were carried out through hemostasis test on mouse femoral artery incision,single-contact test on both broken and healthy dorsal skin of guinea pig,and adsorption test on mouse liver.The results showed that the optimum preparation process of the fish scale collagen composite hemostatic sponge was as following:the ratio of collagen to chitosan was 7∶3,the preparing total concentration was 1.4%,the amount of crosslinking agent was 0.015%and the hemostatic time was(68±9)s.The sponge possessed strong security since there was no sensitization and irritation to the dorsal skin of guinea pig,and it could be assimilated by mouse liver after eight weeks.Therefore,the fish scale collagen composite hemostatic sponge possessed remarkable hemostatic effect,safety performance and biocompatibility.