<p>Benefiting from the precision programmability, excellent biocompatibility and low immunotoxicity of DNA, cavity-engineered DNA nanocages have been intelligently developed to meet various application scenarios such as biosensing, cargo delivery and material assembly. This review first introduces the methods of DNA nanocage self-assembly. Due to the growing application requirements, DNA nanocages with different topologies have been successfully developed based on computer software simulations, including structurally transformable nanocages, multilayered/aggregated DNA nanocages, and large-size DNA origami nanocages. Next, the review focuses on summarizing the functions of DNA nanocages. Compared to other 3D DNA nanostructures, the stable scaffold structure of DNA nanocages protects internal cargo from degradation during transport and provides multiple modifiable sites. Moreover, their size-adjustable cavities accommodate the encapsulation and segregation of cargoes and are expected to provide a confined space for controlled reactions. Then, the popular applications of DNA nanocages that have gained much attention in recent years are summarized, aiming to provide a rich toolbox for developing biomedical application platforms. Finally, based on the current advancements, future directions in this field are envisioned.</p>