Staphylococcus aureus skin infections represent a persistent clinical challenge owing to their high pathogenicity, multidrug resistance, and biofilm-associated recurrence, which collectively impair antibiotic penetration and exacerbate host inflammation. Emodin, a natural anthraquinone with dual antibacterial and anti-inflammatory activities, has shown therapeutic promise but suffers from poor solubility, rapid clearance, and a lack of pathogen specificity, limiting its translational potential. Here, we developed a multifunctional nanoplatform composed of tetrahedral framework nucleic acids (tFNAs), in which Emodin was noncovalently loaded onto a DNA scaffold to enable sustained release, and a Staphylococcus aureus-specific aptamer was displayed to enable targeted bacterial recognition. Notably, this aptamer-guided design is pathogen oriented, aiming for bacteria-associated enrichment in infected wounds rather than targeting host inflammatory markers or specific immune cell subsets.