Medical cotton dressing is cheap and widely used in diversified fields, but in the application of promoting wound healing, the continuous research of multifunctional medical cotton dressing is still of great significance. Here, we developed a fresh type of antibacterial cotton dressing through a succinct strategy based on chemically anchoring polyhexamethylene biguanide (PHMB). Intriguingly, after PHMB modification, the cotton dressing exhibited outstanding antibacterial performance which could maintain >99.99% antibacterial rate after several treatments, including washing 50 times, repeated use 10 times, UV irradiation for 7 days, cationic dyes dying, and conditioned under 90 °C water bath for 2 h. In addition, the water contact angle of cotton dressing increased dramatically from 0° to 111°, which could facilitate bacterial adhesion, thus further enhance the antibacterial efficiency, and easily remove the bacterial debris. Apart from that, the developed cotton dressing showed good cytocompatibility, promoted blood clotting and expression of platelets, and promoted the wound healing process in the infection intervened skin wound model. Taken together, this antibacterial cotton dressing with desirable blood clotting, sustained protection against bacterial infection and bacterial removal features shows the potential to be a candidate for infected skin wound healing.