In this work, the solubility of oxcarbazepine in polymers (PEG 6000, PEG 20000, PVP K25, and PVP K30) and their aqueous solutions was investigated by experimental measurement and thermodynamic modeling. Firstly, the solubility of oxcarbazepine in water and polymers was modeled and the corresponding binary interaction parameters (oxcarbazepine/water and xcarbazepine/polymer) were determined based on the experimental phase equilibrium data. Furthermore, the solubility of oxcarbazepine in the polymer aqueous solution (the mass ratios of polymers in water were 2%, 4%, and 6%) was predicted by the solid-liquid equilibrium (SLE) coupled with the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). It was observed that the predicted results agreed well with the experimental data, and the average relative deviation (ARD) was less than 7%. In this study, the solubility of oxcarbazepine in polymer aqueous solution was successfully predicted through the SLE coupled with the PC-SAFT, which was expected to provide theoretical guidance for the selection of pharmaceutical excipients and the rational design of preparations.