Chemotherapeutic agents and photosensitizers often suffer from poor tumor selectivity, high side toxicity, or low water solubility. To address these problems, various drug delivery systems (DDS) have been explored but most of them are toxic, difficult to synthesize, or of single function. In order to design a highly biocompatible, conveniently prepared, multi-functional drug delivery system, herein, an aptamer of vascular endothelial growth factor (VEGF) and a cytosine (C)-DNA fragment were grafted on the surface of superparamagnetic iron oxide nanoparticles (SPION), and then a chemotherapeutic agent daunomycin (DNM) and a photosensitizer 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP) were self-assembled with the hybridized VEGF-based DNA structure. By loading DNM and TMPyP, the DDS displayed strong chemotherapeutic/phototherapeutic capability against cancer cells via mechanisms such as mitochondrial dysfunction and ROS elevation, which triggered the apoptosis of the tumor cells. The dual delivery of chemotherapeutical agents and photosensitizers with aptamer/C-rich DNA successfully integrated the functions of pH stimuli-responsive drug release and chemotherapeutic/phototherapeutic modalities into one single system and thus could be considered as an ideal drug delivery vehicle with great potential in clinic.