The solubility of etonogestrel in ten different monosolvents [isopropanol, n-propanol, tetrahydrofuran (THF), ethanol, ethyl acetate, methyl acetate, N,N-dimethylformamide (DMF), n-butanol, acetone, and water] and in a binary solvent system of methanol + water has been tested at temperatures from 273.15 to 323.15 K under atmospheric pressure by the gravimetric method. The dissolving capacity of etonogestrel in ten pure solvents and the methanol + water binary system increased with increasing temperature. The order of solubility in pure solvents is ranked as follows: THF > DMF > ethyl acetate > acetone > methyl acetate > n-butanol > isopropanol > n-propanol > ethanol > water. The modified van't Hoff equation, the Buchowski-Ksiazczak.h equation, the Apelblat equation, the nonrandom two-liquid equation, the UNIQUAC equation, the Wilson equation, the Jouyban-van't Hoff equation, and the Jouyban-Apelblat equation were used to describe the solubility data in different solvents. The solubility calculated by the Apelblat model is in good agreement with the experimental data in ten pure and mixed solvents, which provided the basis for the separation and production process of etonogestrel.