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S-nitrosothiols (RSNO) as the potential nitric oxide (NO) storage, transfer and delivery vehicles under physiological condition have been identified as important in a number of disease states. However, a detection and quantification of RSNO method with simple and sensitive in biological media is currently lacking. A novel electrochemical sensing platform based on ionic liquid (IL) and copper porphyrin (PorCu) decorated cuprous oxide (Cu 2 O) nanocomposites was developed to detect RSNO under physiological condition. In this system, RSNO were decomposed by Cu(I) in IL/PorCu/Cu 2 O to release NO, following the generated NO could be oxidized on the electrode to generate current signal. By taking advantage of the synergetic effect of IL, PorCu and Cu 2 O, the sensor exhibited excellent sensitivity and linearity toward various RSNO species in phosphate buffer solution (PBS), pH 7.4. A low detection limit for N-Acetyl-3-(nitrososulfanyl)valine (SNAP), S-nitrosocysteine (CysNO) and S-nitrosoglutathione (GSNO) was 110 nM, 20 nM and 67 nM (S/N = 3), respectively. Furthermore, this method displayed good selectivity, which could be used in complex application. The detection scheme with the features of high sensitivity and ease of operation, implies the potential of IL/PorCu/Cu 2 O for further various complex physiological studies., Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)