Acetaminophen (AC) is one of the most popular pharmacologically active substances used as an analgesic and antipyretic drug. Herein, a new type of hollow Fe3O4-rGO/GCE electrode was prepared for electrochemical detection of AC through a three-step approach involving a solvothermal method for the synthesis of hollow Fe3O4 and the chemical reduction of graphene oxide (GO) for reduced graphene oxide (rGO) and Fe3O4-rGO nanocomposites modified on the glassy carbon electrode (GCE) surface. The as-prepared Fe3O4-rGO nanocomposites were characterized using a transmission electron microscope (TEM), X-ray diffraction (XRD), and a magnetic measurement system (SQUID-VSM). The magnetic Fe3O4-rGO/GCE electrodes were employed for the electrochemical detection of AC using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and square wave voltammetry (SWV) and exhibited an ultra-high selectivity and accuracy, a low detection limit of 0.11 µmol/L with a wider linear range from 5 × 10−7 to 10−4 mol/L, and high recovery between 100.52% and 101.43%. The obtained Fe3O4-rGO-modified GCE displays great practical significance for the detection of AC in drug analysis.