The parameters of preferential solvation of 4-hydroxy-2.5-dimetyl-3 (2H)-furanone (HDMF) in ethanol (EtOH) were derived from its thermodynamic properties of solution by means of inverse Kirkwood-Buff integrals and quasi-lattice-quasi-chemical (QLQC) methods. According to the IKBI method, the preferential solvation parameter δx1,3 of EtOH is negative in water-rich mixtures but positive in ethanol-rich mixtures. It is possible that the hydrophobic hydration around the methyl groups of the HDMF plays a role in the solvation in water-rich mixtures. The greatest EtOH solvation in ethanol-rich mixtures may have been due, mainly, to the effects of polarity and acid-base behavior of the hydroxyl groups in the compound against the most basic solvents in the solution. On the other hand, using the QLQC method, this compound is preferably solvated by the cosolvent in most of the water-ethanol system mixtures.