Studies related to redox reaction of human whole blood with hydrogen sulfide is highly important in biological system (e.g., detoxification of sulfide ion) and there have been several indirect experimental evidences for their interaction. This is the first and direct report for electrochemical oxidation and reduction of sulfide ion on a human whole blood chemically modified electrode system in physiological solution. A specific diffusion controlled electrochemical oxidation signal at 0 V vs Ag/AgCl and reduction signal at -0.5 V vs Ag/AgCl corresponding to the electrochemical conversion of sulfide ion to sulfate and sulfide to sulfur atom respectively by the Blood-Hemoglobin-Fe-III/II redox site were noticed. These reactions are similar to the red blood cell functional behaviours with hydrogen sulfide (exist as HS- in a neutral solution) as detoxification mechanism in the human body. Control results of electrochemical sulfide oxidation/reduction reactions with commercial hemoglobin and heme derivative (hematin) modified electrodes support the observation. Calculated electrochemical sulfide oxidation parameters such as Tafel slope, transfer coefficient (alpha) and heterogeneous rate constant (Andrieux and Saveant model) values are 120 mV decade(-1), 0.5 and 4.77 +/- 1.51 x 10(-6) mot(-1) cm(3) s(-1) respectively. Selective flow injection analysis of sulfide ion (HS-) using the blood chemically modified electrode was demonstrated as a proof of concept for the applicability of the working electrode to analytical application. (C) 2017 Elsevier B.V. All rights reserved.