In this study, we describe a novel method for preparing Y₂O₃@CaO ceramic cores with anti-hydration performance and high-interface stability against interface reaction of Ti-6Al-4V alloys. The effect of Y₂O₃ coating on microstructure, mechanical, anti-hydration properties of ceramic cores and interface reaction with Ti-6Al-4V alloys was studied. The results show that the surface charge of Y₂O₃ and CaO are opposite at the pH value of 13, which might result in an electrostatic force and become the main driving force of Y₂O₃ particles absorb on the surface of CaO particles. The Y₂O₃ coating improved the anti-hydration properties of the CaO-based ceramic cores after sintering at 1450 °C. Meanwhile, the flexural strength improved from 11.2 to 18.8 MPa. At last, the interaction between the ceramic cores and Ti-6Al-4V metal were studied by centrifugal investment casting. Y₂O₃ coating can effectively reduce the interface reaction and the thickness of the interaction layer in the casting was less than 10 μm. The results suggest that the Y₂O₃@CaO ceramic with anti-hydration performance provide excellent mechanical and high-interface stability against interface reaction of Ti-6Al-4V alloys.