DL-Homocysteine thiolactone hydrochloride (one of the derivatives of L-cysteine) solubility in nine neat solvents (methanol, ethanol, isopropanol, ethyl acetate, 1,4-dioxane, acetonitrile, acetone, 2-butanone, and dichloromethane) were determined by the static gravimetric method at the atmospheric pressure from 283.15 to 323.15 K. At the same time, the solubility in the methanol + acetonitrile binary solvent system was determined. From the result of the experiments, the solubilities all increased with the increase of the temperature. And the polarity is one of the important factors affecting solubility. The three-dimensional (3D) Apelblat-Jouyban-Acree model and the Apelblat-Machatha model were used for correlating the solubility data, and the values calculated by the two thermodynamic models were in good agreement with the experimental data.