L-Cysteine methyl ester hydrochloride (one of the derivatives of L-cysteine) solubility in 14 monosolvents (methanol, ethanol, n-propanol, n-butanol, sec-butanol, isopropanol, isobutanol, ethyl acetate, 1,4-dioxane, acetonitrile, acetone, 2-butanone, n-pentanol, and dichloromethane) was determined by the static gravimetric method from 283.15 to 333.15 K under the atmospheric pressure. Meanwhile, its solubility in the binary solvent of ethanol + dichloromethane was measured from 283.15 to 303.15 K. From the experimental results, the solubility increased with increasing temperature. And three kinds of polymorphs appeared in the selected solvent systems, which are named alpha-form, beta-form, and gamma-form. Furthermore, from the results, the main factors affecting solubility are polarity, Hildebrand solubility parameter, and hydrogen-bonding interactions. Six thermodynamic models (the modified Apelblat model, Yaws model, Jouyban-Acree model, Machatha model, Apelblat-Jouyban-Acree model, and Apelblat-Machatha model) were used for correlating the solubility data. The Akaike information criterion method was used to evaluate the thermodynamic models.