Bacterial infections, especially infections caused by multi-drug resistant bacteria, pose a serious threat to human health and bring huge challenges to clinical treatment. The excessive use of antibiotics can easily lead to the emergence of bacterial resistance, which severely limits clinical treatment options. There is an urgent need to develop high-efficiency antibacterial materials and treatment strategies to inhibit infections caused by multidrug-resistant bacteria. In this work, a nanocomposite named Ofloxacin@HMPB@HA(OHH NPs) combined with the laser irradiation was used to reduce the development of drug resistance and accelerate wound healing in a model infected by Klebsiella pneumoniae(K.Pneumoniae). In vitro results showed that compared with OHH NPs or NIR laser irradiation alone, this combination strategy can exert a synergistic effect on anti-K.Pneumoniae by destroying cell integrity with generating ROS and reducing ATP, and also inhibit the development of bacterial resistance. Moreover, in vivo experiments have shown that the system effectively promotes wound healing through killing K.Pneumoniae and promoting the formation of new tissues. In summary, these results indicate that OHH NPs show great potential in the clinical application of bacterial infections.