Herein, we present a simple method to prepare Au nanoparticle-coated, polydopamine-modified poly(lactic-co-glycolic acid) (AuNPs@PDA/PLGA) hybrid capsules for combined ultrasound imaging and high-intensity focused ultrasound (HIFU) therapy. In this approach, PLGA nanocapsules are prepared firstly via a facile and efficient water/oil/water (W/O/W) emulsion strategy, and are then modified with PDA through the self-polymerization of dopamine in a weakly alkaline aqueous environment. Subsequently, chloroauric acid (HAuCl 4 ) solution is added, and AuCl 4 À ions are absorbed on the surfaces of the PDA/ PLGA nanocapsules by the active catechol and amine groups of PDA coatings. Finally, these absorbed AuCl 4 À ions are reduced in situ to AuNPs to form AuNPs@PDA/PLGA hybrid capsules. The in vitroultrasound imaging experiments show that AuNPs@PDA/PLGA hybrid capsules are suitable for ultrasound contrast imaging. Moreover, the potential of the nanocapsules to enhance HIFU therapy is also demonstrated. These results show that ultrasound-guided HIFU therapy ex vivo with AuNPs@PDA/PLGA hybrid capsules is highly efficient on degassed bovine livers due to the high thermal energy accumulation of AuNPs. Thus, the successful integration of the AuNPs and PLGA nanocapsules provides an alternative strategy for highly efficient ultrasound-guided HIFU therapy.