Hollow and porous structured GdVO4:Dy3+ spheres were fabricated via a facile self-sacrificing templated method. The large cavity allows them to be used as potential hosts for therapeutic drugs, and the porous feature of the shell allows guest molecules to easily pass through the void space and surrounding environment. The samples show strong yellow-green emission of Dy3+ (485 nm, 4 F9/2 → 6 H15/2; 575 nm, 4 F9/2 → 6 H13/2) under UV excitation. The emission intensity of GdVO4:Dy3+ was weakened after encapsulation of anticancer drug (doxorubicin hydrochloride, DOX) and gradually restored with the cumulative released time of DOX. These hollow spheres were nontoxic to HeLa cells, while DOX-loaded samples led to apparent cytotoxicity as a result of the sustained release of DOX. ICP measurement indicates that free toxic Gd ions can hardly dissolate from the matrix. The endocytosis process of DOX-loaded hollow spheres is observed using confocal laser scanning microscopy (CLSM). Furthermore, GdVO4:Dy3+ hollow spheres can be used for T1-weighted magnetic resonance (MR) imaging. These results implicate that the luminescent GdVO4:Dy3+ spheres with hollow and porous structure are promising platforms for drug storage/release and MR imaging