Rattle-type hollow nanocapsules are among of the most promising candidates as drug carriers owing to their huge inner space and multifunctional material combination. In this paper, rattle-type hollow CaWO4:Tb3+@SiO2 nanocapsules with a diameter of 100–110 nm and a wall thickness around 10 nm were fabricated. The hollow silica nanospheres were used as nano-reactors and the luminescent core of CaWO4:Tb3+ was post-filled into the nano-reactors by a vacuum nano-casting route combined with a Pechini-type sol–gel method. Subsequently, doxorubicin hydrochloride (DOX), a model of an anti-cancer drug, is loaded into the CaWO4:Tb3+@SiO2 nanocapsules and their cell cytotoxicity, cancer cell uptake and drug release behavior are investigated in vitro. The prepared multifunctional inorganic nanocapsules show a loading capacity for DOX as high as 124 mg g-1 and sustained-release properties. The release profile of the drug from DOX-loaded nanocapsules can last over five days. Besides, the blank CaWO4:Tb3+@SiO2 shows very low cytotoxicity against cancer cell lines (HeLa cell) while the DOX-loaded nanocapsules exhibit relatively high efficiency for killing of HeLa cells. The rapid cancer cell uptake process is observed by confocal laser scanning microscopy. The results indicate that a rattle-type hollow CaWO4:Tb3+@SiO2 nanocapsule has the potential to be used as drug carrier in therapy. Moreover, it is possible to extend the synthetic strategy in this study to other rattle-type multifunctional composites to meet various demands.