From the perspective of developing new tissue engineering epidermal substitutes, collagen and agarose were selected to construct a composite hydrogel to support the growth of epidermal cells. Collagen solution (2%) and agarose solution (2%) were used to investigate the morphology, physical and chemical properties and mechanical properties of the collagen-agarose composite hydrogels with collagen as a control. The biocompatibility of collagen-agarose composite hydrogel with human immortalized epidermal cells (HaCaT) was also examined. The results show that agarose improved the mechanical properties of collagen. The mechanical properties and biocompatibility of the scaffold were balanced when the content of collagen and agarose is 65% and 35%, respectively. The composite hydrogel based on collagen-agarose developed in this study is an ideal epidermal substitute for tissue engineering.