The increasing application of carbon paste electrode (CPE) in the fabrication of electrochemical sensors has motivated researchers to develop new electrode materials. In the present work, Fe3O4 nanoparticles supported on the multi-walled carbon nanotubes and polyacrylonitrile nanofibers (Fe3O4@MWCNTs@PANNFs) was synthesized via the bulk modification approach to detect imatinib (IMA), as an important anticancer drug. The modified CPE materials were characterized by FESEM, FT-IR, Raman spectroscopy, EDX analysis, XRD, CV, and EIS techniques. The electrocatalytic behavior of IMA at the surface of the modified CPE was studied using a differential pulse voltammetry method. Taking advantages of the electrocatalytic behavior of Fe3O4 nanoparticles and MWCNTs, as well as the large surface area of PANNFs, an applicable-modified CPE was introduced for electrochemical determination of IMA with high sensitivity. The anodic peak currents of IMA increased linearly within the concentration ranges of 0.0017-0.8500 mu M, along with detection limits of 0.4 nM. In addition, the oxidation mechanism of IMA was proved by electrochemical simulation. Finally, the Fe3O4@MWCNTs@PANNFs/CPE was employed to the electrochemical determination of IMA in urine samples. Graphic abstract