In this paper, size-controlled morphologies of (Y, Gd)VO4 and (Y, Gd)VO4:Ln3+ (Ln = Eu, Yb, Er, and Ho) were obtained via a facile hydrothermal route, and their properties for drug delivery and photoluminescence were investigated. Monodisperse ellipsoid-like hollow (Y, Gd)VO4 were designed by employing (Y, Gd)(OH)CO3 colloidal spheres as a sacrificial template and NH4VO3 as a vanadium source, and the formation mechanism could be interpreted by the Kirkendall effect. The control of particle size for hollow (Y, Gd)VO4 was realized, facilitating their practical application. Mesoporous core–shell structured (Y, Gd)VO4:Ln3+@nSiO2@mSiO2 were designed to improve the properties for drug release. Typically, red emission of YVO4:Eu3+ predominated under 465 nm excitation; the upconversion spectra of YVO4:Yb3+, Er3+ and YVO4:Yb3+, Ho3+ revealed green and red color upon 980 nm excitation, respectively. The biocompatibility and drug release evaluations indicate the potential biological applications of the samples.