Nowadays targeted delivery of drugs is one of the most important ways to overcome the disadvantages of classical chemotherapy. In this study, smart pH-sensitive Fe3O4/PEC/Imatinib nanoparticles were synthesized, and their performance was investigated. The proposed therapeutic system was prepared by covering the surface of magnetic Fe3O4 nanoparticles with PEC and then Imatinib. The structural features of the synthesized drug delivery system were characterized by various techniques including X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared (FTIR) spectroscopy and vibrating sample magnetometry (VSM). The formulated Imatinib-loaded modified PEC-magnetic nanoparticles demonstrated a proper encapsulation and loading performance combined with magnetic reactivity. It is noteworthy that the use of magnetic Fe3O4/PEC can help to the precise and facilitated release of Imatinib drug to the specific tissue by applying the field of an external magnet. This nanocomposite has a component drug efficiency (78 wt%), and proper drug loading (27 wt%) and also, in this drug delivery system, the drug release was sensitive to pH changes. The amount of Imatinib release from Fe3O4/PEC nanoparticles was much faster in lower pHs (100%) which indicates Fe3O4/PEC/Imatinib is a proper nanosystem which acted successfully in different cancerous cells. Hence, this system can release Imatinib selectively and reduce cytotoxic effects. Also, the cytotoxic activity of imatinib and this magnetic nanocarrier were studied against GC1415 and GC1436 cell lines under in vitro environment. According to the obtained consequences of cytotoxicity investigations, the loading of Imatinib on the surface and in the layers of Fe3O4/PEC nanoparticles induces a significant improvement in the anticancer effect of Imatinib drug.