The solubility of trimetazidine hydrochloride in 12 neat solvents namely ethanol, methanol, isopropyl alcohol, n-propanol, acetone, toluene, 2-butanone, ethyl acetate, n-butanol, acetonitrile, N,N-dimethylformamide (DMF), and 1,4-dioxane and binary liquid mixtures methanol + (ethanol, DMF, or ethyl acetate) was measured using the isothermal method over the temperature range from 278.15 to 323.15 K under local atmospheric pressure of 101.2 kPa. The observed mole fraction solubility was the largest in methanol and smallest in toluene. The experimental data in monosolvents was correlated through the Apelblat equation; while in mixed solvents, by the van't Hoff-Jouyban-Acree model, Jouyban-Acree model and Apelblat-Jouyban-Acree model. Consequently, for the selected monosolvents, the largest relative average and root-mean-square deviations were 0.79% and 0.227 x 10(-4), respectively; and for the binary solvent mixtures, 3.00% and 2.22 x 10(-4). Solvent-solvent and solute-solvent interactions were analyzed in the 12 net solvents with linear solvation energy relationship analysis. The solubility in monosolvents depends significantly upon the Hildebrand parameter and nonspecific dipolarity/polarizability interactions. The values of log x(12) deviated from the mean values of log x(12) in the monosolvents. Results were interpreted based on different modes of the solvation interactions.