Electrochemical properties of regorafenib (REG) were studied in 0.1 M Britton-Robinson buffer-methanol solutions (3 : 2, v/v) with pH between 3 and 8 at carbon paste electrode by cyclic and differential pulse voltammetry. The results exhibited irreversible anodic peak at about 0.90 V vs. Ag/AgCl, NaCl (3 M). The anodic peak was found to be diffusion-adsorption controlled. Mechanism of REG electrochemical reaction was studied by performing density functional theory computations and mass spectrometric analysis. A validated differential pulse voltammetry (DPV) technique for REG determination was performed. The calibration curve of REG on carbon paste electrode was linear in the concentration range of 0.5-13 mu g/mL and limit of detection was 0.10 mu g/mL. The recommended DPV method was used to detect REG in spiked plasma and urine specimens and average recoveries were 94%.