A novel drug-delivery vehicle for mitochondria-targeted chemo-photothermal therapy was demonstrated. A cytochrome c-specific binding aptamer was employed to make the mesoporous silica-encapsulated gold nanorods efficiently accumulate in the mitochondria of cancer cells. This nanocarrier can load various hydrophobic therapeutic agents acting on mitochondria to enhance the therapeutic efficiency and simultaneously depress the toxic side effects. In addition, near-IR treatment could induce cytochrome c release and initiation of the mitochondrial pathway of apoptosis. Importantly, this multifunctional platform could integrate targeting, light-triggered release, and chemo-photothermal therapy into one system. We hope that such a system could open the door to the fabrication of a multifunctional mitochondria-targeted drug-delivery vehicle for cancer therapy.