Herein, we report a facile preparation of vertically oriented reduced graphene oxide sheets (VrGO) supported on
a palladium nanoparticles-decorated graphite electrode. The electrode is fabricated by a simple two electrodeposition steps method. The designed electrode BEFD&VrGO@PdNPs successfully provides an open structure of rGO layer exposing palladium nanoparticles (PdNPs) to the solution, leading to formation of a uniform distributed vertically oriented rGO (VrGO) due to the high surface area of palladium-decorated PGE substrate. The fabricated electrode was successfully used for determination of sorafenib (SOR); an anti-cancer drug. Using square wave voltammetric method (SWV), the fabricated electrochemical sensor succeeds to monitor the electro-oxidation of SOR with a low limit of detection of 9.9 x10? 10 M and ultrahigh sensitivity of 237 μA nM? 1cm? 2 over a linear concentration range of 3–120 10? 9 M with an excellent correlation coefficient. Additionally, the performance of the modified electrode has been successfully tested by real-time monitoring of SOR in pharmaceutical tablets, human plasma, and human urine without any interference from complex matrices.