Methicillin-resistant Staphylococcus aureus (MRSA) have become increasingly prevalent as nosocomial pathogens, especially in burn patients, which is the leading cause of their death. A drug delivery system of chitosan-collagen hydrogel incorporated with lysostaphin (CCHL) based on the lysostaphin gauze was developed for MRSA infected burn wounds. CCHL scaffold consisted of numerous interconnected sphericles and tubular bodies with an average diameter of 100-200 µm, 20-60-fold swelling, high water retention capacity, and cell proliferation properties. The minimal inhibitory concentration of CCHL was 0.053 U/mL. By the second week after its application on MRSA infected third-degree burn wounds, no bacteria could be detected and the burn wounds had started healing. Therefore, CCHL should be studied further as a promising candidate of burn treatment dressing against MRSA infections for clinics.