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Collagen (Col)-based composite hydrogels have attracted wide attention because of the additional properties that the second component brings to the hydrogel. Here we reported self-assembly of collagen and cross-linking of alginate with [Ca.sup.2+] to prepare a novel composite hydrogel with Tilapiaskin-derived collagen and alginate for efficient wound repairing as the wound dressing. The composite hydrogels exhibited higher water content, coupled with a significant increase in water retention rates upon the incorporation of alginate. As the concentration of alginate rose, the cross-linking network became tighter, thereby not only modifying the internal structure of the hydrogel but also enhancing its mechanical strength. Moreover, the collagen degradation rate in the composite hydrogels was greatly reduced through addition of alginate, and the collagen-alginate composite hydrogels exhibited low cytotoxicity, and improved wound healing efficacy, accelerating the maturation of skin attachments and the secretion of vascular endothelial growth factor (VEGF). These results suggested that the composite hydrogel formed by fish-derived collagen and alginate held promising potential as a wound dressing for challenging and refractory wounds. KEYWORDS alginate, characterization, collagen, composite hydrogel, wound dressing Highlights * Tilapia-skin-derived collagen/alginate hydrogels was prepared by selfassembly and cross-linking method. * The introduction of alginate improves the mechanical strength of collagen hydrogel. * The addition of alginate can slow down the degradation of collagen. * The composite hydrogels retain high water content and low cytotoxicity. * The composite hydrogels can promote wound healing significantly., 1 | INTRODUCTION Refractory wounds, such as severe frostbite, burns and ulcers, can cause full-thickness skin damage and are difficult to repair, (1,2) which brings great pain to patients, and [...]