In this paper, a strategy was developed for fabricating uniform polydimethylsiloxane (PDMS) microcapsules with eccentric and core-centered internal hollow structures, which can be employed as a novel controlled-release system for site-specific drug delivery under ultrasound regulation. This strategy involves the use of a microfluidic device, through which three phases (i.e., an inner water phase containing drug molecules, a middle oil phase of PDMS solution, and an outer water phase) were delivered at independently adjustable flow rates, allowing the formation of water-in-oil-in-water (W/O/W) emulsion droplets in a microfluidic device. After baking the as-prepared microcapsules, microcapsules with different inner hollow cores were obtained. The sizes of the inner hollow structures could be tuned, leading to a series of microcapsules with different densities. The densities of these microcapsules were all lower than that of water, which showed a long gastric residence time. Most interestingly, eccentric hollow microcapsules with well-controlled sizes and shapes were also prepared using this method. The eccentric and core-centered hollow microcapsules demonstrated triggered and controlled the release of encapsulation under ultrasound, for which the release profiles were consistent with the theoretical simulation. The results showed that the microcapsules had all the properties of a floating drug delivery system and controlled release system, and demonstrated great potential to be used for controlled release, in particular, for the delivery of drugs that are absorbed primarily in the upper segments of the gastrointestinal tract.