The main objective of this work is to continue with a series of electrochemistry studies of mixtures of ionic liquids and water as a solvent to provide accurate data for future particular applications [Amado-Gonzalez et al. J. Chem. Eng. Data 2017, 62, 752]. The mean activity coefficients for NaCl in [2-hydroxyethylammonium butyrate (2-HEAB) + H2O] as a solvent mixture were determined by cell potential measurements: Na–ion selective electrode (ISE)|NaCl (m), 2-HEAB (w), H2O (1 – w)|Cl–ion selective electrode (ISE) at molalities from 0.10 to 3.20 mol·kg–1 at 298.15 K. Different weight fractions (w) of 2-HEAB with w = 0.01, 0.05, 0.1, 0.2, 0.3, and 0.4 were used. At higher concentrations of w = 0.40, NaCl is salting out by 2-HEAB in water. The Pitzer ion interaction parameters β0, β1, and Cγ were used to find the values of osmotic coefficients, solvent activity, and the excess Gibbs free energy for the mixed electrolyte system. The results may be interpreted by the clathrate-like formation of 2-HEAB + water. A qualitative description of the relation between water and the 2-HEAB was done using the general AMBER force field (GAFF).