Collagen is highly valued both as a food additive and a functional food ingredient. It is generally extracted by treatments with acid or alkali, enzyme, and microorganisms. However these methods are generally batch type, time-, energy-, reactant-, and cost-consuming. Extrusion is widely used in the food industry, and offers many advantages, such as ease of operation, continuous production, high yield, and little waste. In this study, we developed a novel extrusion–hydro-extraction (EHE) process for extraction of collagen from tilapia fish scale. Extruded scale samples had a 2–3times higher protein extraction yield than that of non-extruded scale samples. All extracts contained hydroxyproline (61–73 residues/1000 residues) and hydroxylysine (5–6 residues/1000 residues) and were identified as type-I collagens by FTIR, SDS–PAGE, and molecular weight distribution analyses. The physicochemical studies revealed that extracted collagens could have promising applications in the food, medical, and cosmetic industries.