In this work, we report a facile solution-phase synthesis of hollow cubic phase α-NaYF4
nanoparticles by a controlled ion exchange process from cubic phase Y2O3 nanospheres. We demonstrate that hollow nanoparticles with controlled size are formed owing to the nanoscale Kirkendall effect. The formation mechanism was studied with the XRD, STEM, and EDS line scanning characterization. The crystal structure similarity between the parent and the final product is essential for framework and morphology preservation. Although the sphere particles are polycrystalline and composed of the nanocrystals, the cubic structure of α-NaYF4 nanocrystals displays a noticeable structure similarity with Y2O3, which we believe facilitates ion exchange between the primary nanocrystals and preservation of the secondary sphere morphology. The multicolor upconversion (UC) fluorescence (PL) was successfully realized in the Yb3+/Er3+(Tm3+) codoped α-NaYF4 hollow nanospheres by excitation in the near-infrared (NIR) region. The various UC emission ratios of the samples were investigated as a function of hydrothermal reaction time to research the UC properties of the products and to further demonstrate the thermodynamic driving solution ion-exchange process.