Fulfilling the purpose of developing a NP with theragnostic capabilities, the current study describes the synthesis of an aptamer-functionalized PEG-coated SPION/mesoporous silica core-shell nanoparticle for concurrent cancer targeted therapy and magnetic resonance imaging. SPIONs were synthesized according to a thermal decomposition method and served as cores for SPION/mesoporous silica core/shell nanoparticles (MMSNs). Doxorubicin was then successfully loaded in MMSNs which were then coated with di-carboxylic acid functionalized polyethylene glycol (PEG-MMSNs). AS1411 aptamers were at the end covalently attached to NPs (APT-PEG-MMSNs). The mean diameter of synthesized NPs was about 89 nm and doxorubicin encapsulation efficacy was ≈67.47%. Results of MTT based cell cytotoxicity assay demonstrated a significantly higher toxicity profile for APT-PEG-MMSNs against MCF7 cells compared to non-decorated MMSNs, while no significant differences were spotted against NIH-3T3 cells. Meanwhile, formation of protein corona around APT-PEG-MMSNs in biological medium significantly attenuated observed cytotoxicity against MCF7 cell line. Examining NPs uptake by MCF7 cells using confocal laser scanning microscopy also confirmed superiority of APT-PEG-MMSNs over PEG-MMSNs. Finally, APT decorated NPs induced highest signal intensity reduction in T-weighted images during MRI assay. In conclusion, developed NPs may serve as promising multifunctional vehicles for simultaneous cancer targeted therapy and MRI imaging.