A simple, facile and sensitive method for the fabrication of molecularly imprinted sensor is proposed for the determination of hydrochlorothiazide (HCTZ). The sensor is fabricated by the deposition of iron oxide nanoparticles followed by the electropolymerization of melamine monomer in the presence HCTZ at the surface of edge plane pyrolytic graphite. The surface of the imprinted sensor was characterized by using Field Emission Scanning Electron Microscopy, Energy dispersive X-ray analysis, Electrochemical Impedance Spectroscopy, X-ray diffraction, Cyclic Voltammetry and Square Wave Voltammetry. The oxidation of HCTZ occurred in a single, well-defined peak and the peak current was dependent on the concentration of HCTZ in the range 25 x 10(-9)-10 x 10(-6) M. The sensitivity and limit of detection (3s/b) were found to be 2.342 mu M/mu A and 4 nM respectively. The proposed method was applied for the determination of HCTZ in the presence of common metabolites present in human system. The obtained results indicated that uric acid, ascorbic acid, hypoxanthine and xanthine did not interfere up to 100 fold concentration. The imprinted sensor was successfully applied for determination of HCTZ in real samples such as pharmaceuticals and urine samples. (C) 2017 The Electrochemical Society. All rights reserved.