We developed a PEI-functionalized hafnium oxide (HfNP) nanoplatform for enhanced radiotherapy. Through phase-transfer ligand exchange, we replaced hydrophobic ligands with polyethyleneimine (PEI) to impart hydrophilicity and cationic potential. FT-IR and TGA analyses confirmed the robust polymer coating. The PEI shell acted as a critical gene vector, efficiently condensing Bcl-2 siRNA via electrostatic interactions. Optimization studies indicated that an N/P ratio of 28 yielded stable polyplexes with superior cellular uptake. The platform combined HfNP-mediated radiosensitization with PEI-facilitated Bcl-2 silencing, significantly overcoming radioresistance. In a colon cancer model, this synergistic approach achieved 80% tumor growth inhibition. This study demonstrates the efficacy of PEI surface engineering in converting inorganic radiosensitizers into multifunctional polymeric gene delivery systems.