Hydrogels demonstrate superior properties that favors wound healing and have been widely used in clinical settings for wound dressing applications. However, commercial hydrogel dressings often lack flexibility/adhesiveness, and do not conform well to irregular skin surfaces of complex wounds and/or wounds near joints. As a result, the wound is likely to be exposed to potential bacterial invasion. Herein, we designed and developed a mechanically flexible and self-adhesive polyurethane - poly(acrylamide) (PU-PAAm) hydrogel for wound healing applications. The hydrogel can be cured from a novel waterboune emulsion within 90 s under UV irradiation. The PU component within the PU-PAAm hydrogel plays a “bridging” role that accelerates the formation of an interpenetrating polymer network (IPN), which consists of a physically crosslinked PU network trapped within a chemically crosslinked PAAm network. The unique IPN structure endows the hydrogel with superior stretchability and ductility. The hydrogen bonding formation and electrostatic interaction between the hydrogel and skin ensure strong adhesion without causing irritation to skin upon dressing removal. Animal studies further confirmed the PU-PAAm hydrogel’s remarkable skin regeneration capability. This work shows our new hydrogel holds a promising prospect for treatment of complicated or challenging wounds such as burns and chronic wounds.