Objective To review the lately new progress of fish collagen as biomedical materials, and then analyze feasibility and risk management of its application as a substitute of collagen originated from mammals in clinical practice. Methods Based on extensive research on new application and investigation of fish collagen, the paper was prepared to bring comprehensive analysis of its research and application status, and then several key points were focused on. Results Fish collagen has been proved to be a novel collagen of rich source, low risk of virus transmission, low biological risk, less religious barrier, and high biocompatibility. Fish collagen has promising prospect when applied in clinical practice as novel collagen especially as a substitute of collagen derived from mammals. However, very few related translational medicine research of fish collagen has been reported up to now in China. Conclusion As a novel potential substitute of collagen source derived from mammals, fish collagen is concerned to be clinical feasible and necessary in translational medicine. However, massive applied basic researches should be focused on in the further investigations.