Specific anion effects on the thermodynamics of caffeine partitioning between aqueous and cyclohexane phases were studied in the presence of 11 sodium salts by utilizing UV-vis spectroscopy. It is observed that weakly hydrated anions such as ClO4-, SCN-, and I- salt caffeine into the aqueous phase and increase the standard Gibbs free energy for caffeine transfer. On the other hand, well-hydrated anions such as CO32- and SO42- salt caffeine molecules out of the aqueous solution and promote the transfer process. Results suggest that weakly hydrated anions associate with the hydrophobic patches of caffeine including three methyl groups and a flat heteroatomic ring to solvate caffeine molecules. Well-hydrated anions are excluded from the caffeine surface to salt caffeine molecules out of aqueous solution. Moreover, the enthalpy and entropy of caffeine transfer were obtained by measuring the standard Gibbs free energy for caffeine transfer at varied temperatures. The transfer of caffeine from the aqueous to cyclohexane phase was an endothermic process driven by the entropy of caffeine transfer. However, the trend in standard Gibbs free energy across the Hofineister series was determined by the enthalpy of caffeine transfer. These results provide an enthalpic origin to explain the Hofineister trends in aqueous solution.