This study presents a new electrochemical sensor (NiO-ERGO/SPE) for sensitive and selective detection of epinephrine (EPI) on the screen-printed electrode (SPE) which is modified with a nanocomposite film consisting of electrochemically reduced graphene oxide and NiO nanoparticles. After surface functionalization, structural and electrochemical characterization of NiO-ERGO film, DPV signals of NiO-ERGO/SPE towards the oxidation of EPI exhibited a linear correlation in the concentration range of 0.025 mu M to 175 mu M with a detection limit of 0.015 mu M, which reveals NiO-ERGO film is manifested a good electrocatalytic activity for EPI detection compared with the previous reports. The selectivity of NiO-ERGO film was also tested on a very wide scale of possible interferents (ascorbic acid, uric acid, dopamine, lactic acid, phenylalanine, tyrosine, tryptophan, Li+, Na+, K+, Ca2+, and Zn2+). Moreover, to evaluate the applicability of the proposed sensor for real sample analysis, NiO-ERGO/SPE was successfully utilized for the determination of EPI in pharmaceutical samples.