A europium selective PVC membrane sensor based on 4-methylphenylisothiocyanate (4-MePIC) as a suitable neutral ionophore is introduced. The semiempirical PM6/SPARKLE calculations were performed to investigate the interaction between the 4-MePIC ligand, Eu(III) and interfering cations. The obtained results were used to predict the selectivity of the proposed sensor. The standard enthalpy of reaction has been used to predict the selectivity of the 4-MePIC ligand to a particular cation, except when the complex formation was controlled by the kinetic parameters. The computational data have been shown that the 4-MePIC ligand could be used as a suitable neutral ionophore in fabrication of a Eu(III) ion selective electrode. The nephelauxetic parameter indicates a significant covalent character in the Eu(III)- ionophore complex. The proposed sensor has a very fast response time with a near Nernstian response of mV decade for Eu(III) over a concentration range from to M with a detection limit of M. It was applied for Eu(III) determination in various synthetic and mouthwash samples with satisfactory results.