Abstract: The electrocatalytic oxidation of hypoxanthine (Hx) by Ru(bpy)32+ (bpy = 2,2′-bipypyridine) on an indium-tin oxide (ITO) electrode upon incorporation of tris(hydroxymethyl)aminomethane (Tris) has been investigated. The addition of Tris is found to obviously promote the electrocatalytic oxidation of Hx by Ru(bpy)32+ on the ITO electrode. The electrocatalytic oxidation of Hx is influenced by scan rate, pH value and Hx concentration. The XPS analysis reveals the presence of following chemical reactions between the oxidized products of Hx and Tris. Taken together, the electrochemical oxidation of Hx in Tris-containing buffer solutions is attributed to an EC′C mechanism, which is a special type of following chemical reaction coupled to the homogeneous electrocatalysis. In buffer solutions containing 10 mmol?L?1 Tris/50 mmol?L?1 NaCl (pH 7.2), the electrocatalytic currents increase linearly with increasing Hx concentration in the range from 0.1 μmol?L?1 to 0.15 mmol?L?1. The correlation coefficient is 0.991 and the detection limit of Hx is 0.12 μmol?L?1 (S/N = 3).