Lanthanide upconversion nanoparticles (UCNPs) have beenextensivelyexplored as biomarkers, energy transducers, and information carriersin wide-ranging applications in areas from healthcare and energy toinformation technology. In promoting the brightness and enrichingthe functionalities of UCNPs, core-shell structural engineeringhas been well-established as an important approach. Despite its importance,a strong limiting issue has been identified, namely, cation intermixingin the interfacial region of the synthesized core-shell nanoparticles.Currently, there still exists confusion regarding this destructivephenomenon and there is a lack of facile means to reach a delicatecontrol of it. By means of a new set of experiments, we identify andprovide in this work a comprehensive picture for the major physicalmechanism of cation intermixing occurring in synthesis of core-shellUCNPs, i.e., partial or substantial core nanoparticle dissolutionfollowed by epitaxial growth of the outer layer and ripening of theentire particle. Based on this picture, we provide an easy but effectiveapproach to tackle this issue that enables us to produce UCNPs withhighly boosted optical properties.