In this work, a multifunctional drug delivery system (DDS) composed of mesoporous hollow silica nanorod core and luminescent Gd2O3:Eu shell (MHSNR@Gd2O3:Eu) was fabricated and applied for optical imaging and drug carrying. The formation process, phase and morphology of the DDS were investigated. The results show that the multifunctional DDS possess uniform core-shell hollow structure, in which the core length of the hollow silica nanorods as approximately 400 nm and a width of approximately 150 nm and the Gd2O3:Eu shell was approximately 30 nm thick. Due to the doping of the Eu3+, the as prepared MHSNR@Gd2O3:Eu emitted bright red light. The in vitro assays with NCI-H460 lung cancer cells domenstrated that the as-obtained MHSNR@Gd2O3:Eu could rapidly and massively enter the cell. Using ibuprofen as a model drug, the release process of the synthesized MHSNR@Gd2O3:Eu was monitored in-vitro. In particular, as the amount of ibuprofen released increases, the photoluminescence intensity of DDS increases. Thus,it is possible to monitor and track the release process through changes in luminous intensity. In summary, it is expected that MHSNR@Gd2O3:Eu may be applied in drug carrying, luminescent tracking and monitoring, and optical imaging. Furthermore, this work provides a reliable approach for the design and preparation of silica/RE2O3 nanocomposite with mesoporous hollow rod-like structures.