For preparation of an ideal wound dressing, a series of novel polyurethane-based asymmetric membranes with acetic starch and poly (ethylene glycol) as fillers were successfully fabricated by a combination of polymer-filler hybridization and immersion precipitation phase inversion. These resultant polyurethane-based asymmetric membranes consisted of an integral and dense skin layer supported by a porous sublayer as designed. The porosity and internal substructure of asymmetric membranes could be controlled by adjusting species and amount of fillers. The polyurethane-based asymmetric membranes showed promoted fluid absorption capability and controlled water vapor transmission, but could inhibit exogenous microorganisms invasion deriving from its dense skin layer. In vitro biodegradation assay indicated that the polyurethane/acetic starch composite membrane exhibited faster degradation behavior. These results indicated that the polyurethane-based asymmetric membranes prepared in this study has potential for application as an ideal wound dressing.