Because of the abuse of antibiotics and threats of antibiotic resistance, bacterial infection is still one of the most difficult issues to be resolved. Thus, it is of great significance to explore novel antibacterial agents. In this paper, we investigated a type of silica-coated gold–silver nanocages (Au–Ag@SiO₂ NCs) as antibacterial candidates. Their intrinsic characteristics of photothermal property and sustained release of Ag ions were fully exploited for near-infrared (NIR)-induced combined anti-infective therapy. The broad-spectrum antibacterial property of the as-prepared Au–Ag@SiO₂ NCs was confirmed in vitro against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli). In addition, Au–Ag@SiO₂ NCs exhibit effective treatment of the S. aureus biofilm with the assistance of NIR irradiation. More importantly, we assessed the in vivo antibacterial efficacy of Au–Ag@SiO₂ NCs against S. aureus, which demonstrated sustainably enhanced therapeutic effects on a rat model with wound infection.