Conventional wound healing materials suffer from low efficiency, poor mechanical strength, and nontunable properties. Responsive hydrogels are appealing candidates for tissue engineering. Herein, we developed a double-cross-linked hydrogel system composed of hyperbranched PEG-based polymer, comprising pre-cross-linked acetal structure and numerous terminal acrylate groups, which can form hydrogels in situ and can be further strengthened by UV irradiation. The hyperbranched glycidyl methacrylate-co-poly(ethylene glycol) diacrylate polymers (HB-GMA-PEGs) were first synthesized via in situ deactivation enhanced atom transfer radical polymerization (DE-ATRP). A series of pre-cross-linked materials were achieved after postfunctionalization. The material can absorb a high amount of water to form hydrogels, and the gel stiffness was evaluated in detail before and after UV irradiation. The in vitro cytotoxicity experiments were conducted with the resulting materials and have demonstrated their good biocompatibility. The results indicate that this type of hydrogel with high water uptake capacity has appealing potential as a responsive biomaterial for wound closure.