Sorafenib (SORA) has clinical activity against several tumor types. Carbon paste electrode modified with natural sodium montmorillonite clay (Na-MMT/CPE) was used as a sensor for sensitive and selective determination of SORA drug using square-wave adsorptive anodic stripping voltammetry (SW-AdASV). Unmodified CPE as well as the modified one were characterized using scan electron microscopy (SEM), N-2 sorption isotherms (BET) and electrochemical impedance spectra (EIS). In spite of the very low conductivity of Na-MMT, a shift in the peak potential to less positive and about two times enhancement in the peak current were observed at 5% (w/w) Na-MMT/CPE compared to that at bare CPE, reflecting electrocatalytic activity of Na-MMT toward oxidation of SORA. This may be attributed to strong adsorptive property of Na-MMT due to its high surface area or specific bonding reactions of SORA with the functional groups at the edges of clay sheets. The method was employed successfully to determine SORA in its pharmaceutical formulation (Nexavar tablets). Detection limit of 1.5 x 10(-10) M was also achieved in human serum. The described method is reliable, simple and sensitive enough for assay of SORA in real plasma samples, pharmacokinetic studies, quality control and assurance of the drug in industry and in clinical laboratories. (C) 2016 The Electrochemical Society. All rights reserved.