The solubility of silybin in aqueous hydrochloric acid solution has been measured at temperatures range from 293.15 to 313.15 K. Experimental result shows that the solubility increase with the increase of both temperature and PH value. The solubility data was analyzed by a general salt-effect rule and a hydration-ionization model. We have found that the salt-effect rule is obeyed for pH < 3 where silybin is salted out. We have also found that the salt-effect rule is broken for pH > 3 where the concentration of hydrogen ion is very low. The break down of salt-effect rule has been explained by employing a model of molecular hydration-ionization where quantum chemical calculation was performed to support this model by optimizing the geometries of silybin-water complex. Based on this model, the break down of the salt-effect rule is caused by that silybin's acidity increases with the increase of the pH value, which leads to the increase of the solubility at the higher pH regime. The predicted pKa also agrees well with the experimental result. (c) 2007 Elsevier B.V. All rights reserved.