The solubility of two erlotinib hydrochloride polymorphs (form A and form B) in methanol, ethanol, isopropanol, acetone, methyl ethyl ketone, and methyl isobutyl ketone from 273.15 to 323.15 K were determined by means of high-performance liquid chromatography (HPLC). The modified Apelblat equation and the Buchowski–Ksiazczak λh equation were used to correlate the experimental solubility data. The results showed that the solubility of both forms generally increased with the temperature and at a given temperature decreased with the increase of the carbon number of alcohols; furthermore, methyl isobutyl ketone showed the largest solubility in the studied ketones. Meanwhile form A had a higher solubility than form B which demonstrated that form A was the metastable form. Furthermore, both models mentioned above gave satisfactory correlation results, in which the modified Apelblat equation worked better than the Buchowski–Ksiazczak λh equation.