A novel acetaminophen (AP) sensing upon modification with palladium/multi-walled carbon nanotubes composite (Pd/MWCNTs) has successfully developed. The Pd nano-particles were deposited on the MWCNTs by one-step reduction and the modified electrode was fabricated by a simple drop-casting approach. The structure and morphology of Pd/MWCNTs composite were characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. The composite possesses an appreciable specific surface area, demonstrated unsurpassed electrochemical performance in the oxidation of AP. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were performed to investigate the electrochemical behavior of AP on the surface of modified electrode. The oxidation peak current of the as prepared sensor showed an acceptable linear response from 0.5µM up to 100 µM with a detect limit of 0.13 µM(S/N=3). Additionally, The proposed sensor displayed a good recovery in real sample detection. The excellent electrochemical behavior toward oxidation of AP designates that Pd/MWCNTs composite potentially provides a promising platform for facile fabrication acetaminophen sensor and further application.