The swelling curves of poly-N-isopropylacrylamide (PNIPAm) hydrogels in ethanol/water mixtures were determined. A molecular thermodynamic model for swelling behavior of temperature- and solvent-sensitive hydrogels in solvent mixtures was developed by integrating a modified multiple lattice model developed previously for the mixing term and the Flory's Gaussian chain model for the elastic term. Three energy parameters and one volume parameter are included in this model for gel/solvent mixtures systems. Three of the four parameters can be determined from the swelling behavior of hydrogels in pure solvents. The energy parameter measuring the interaction between the two solvents is adjustable and expressed as a quadratic form of the inverse temperature. The calculated results for the swelling curves of PNIPAm hydrogels in ethanol/water mixtures at different temperatures are in good agreement with the experiments. In addition, the equilibrium concentrations of solvent mixtures inside and outside hydrogels can be predicted by this model, which is important for the application of hydrogels. (C) 2010 Elsevier Ltd. All rights reserved.