Here we report on a high-performance electrochemical sensor for the sensitive detection of acetaminophen based on graphene, which was simultaneously electrochemically reduced and deposited onto a glassy carbon electrode (GCE). The electrocatalytic properties of the electrochemically reduced graphene (ERG) toward the oxidation of acetaminophen were analyzed via cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometry. For comparison, various ERG/GCEs were prepared with different electrodeposition cycles to optimize the amount of the ERG. Our experimental results showed that the optimized ERG/GCE possessed robust activity in the electrochemical oxidation of acetaminophen, leading to the development of highly sensitive electrochemical sensor for its detection. An extremely low detection limit of 2.13 nM and a wide linear detection range of from 5.0 nM to 800 mM were achieved via the combination of the amperometric technique and DPV. The developed electrochemical sensor was further employed for the determination of acetaminophen in human serum, with excellent recovery, ranging from 96.08% to 103.2%. The fabricated electrochemical sensor also demonstrated high selectivity, stability and reproducibility. The wide linear detection range obtained in this study for the detection of acetaminophen showed strong potential as a promising sensing technique for pharmaceuticals, in terms of quality control and in clinical laboratories for acetaminophen as relates to the determination of hepatotoxicity. (C) 2014 Elsevier Ltd. All rights reserved.