The fast and efficient selection of food-approved solvents is required for a growing number of flavonoids that are continuously being tested for their nutraceutical properties. Solid-liquid equilibrium is an essential source of information for the design of extraction, precipitation, or crystallization processes in the food industry. In this context, the nonrandom two-liquid segment activity coefficient thermodynamic model showed to be an appropriate tool to represent the solubility of several key flavonoids (apigenin, genistein, hesperetin, luteolin) in pure solvents, suggesting its ability to predict solubility in solvents not considered during the correlation procedure. For substances with unknown melting properties the reference solvent approach was successfully applied. Additionally, new solubility data of S-hesperetin in the pure solvents acetone, ethanol, ethyl acetate, methanol, and acetonitrile was measured, between 25 and 40 °C, by the shake-flask method.