The gas-phase direct epoxidation of propylene using molecular oxygen (DEP), a process deemed as the 'dream reaction' for propylene oxide (PO) production due to its efficiency and environmental benefits, continues to attract substantial research interest. In this contribution, we have engineered a series of Cu2O nanocatalysts by employing ligand-protection/selective facet-etching technique. Among these, the internally hollow Cu2O nanoframes, featured by an expanded specific surface area and a prevalence of {110} sites, achieved triple-win in activity, selectivity, and stability, with an optimal PO formation rate of 0.18 mmol gcat-1 h-1 and a selectivity of 83.8% at 175ºC. In addition, long-term tests confirmed that these internally hollow nanoframes maintained the high activity and selectivity for over 300 minutes. Further characterizations combined with density functional theory calculations confirmed that the unique atomic arrangement of copper and oxygen on the Cu2O {110} facet facilitated the formation of chemically adsorbed oxygen species and propylene oxide as well. We anticipated that the ligand-protection/selective facet-etching approach may serve as a versatile method for fabricating well-defined catalyst architectures.