The basis of purification and further theoretical studies of iohexol is the solubility in different solvents. The solubility of iohexol in 12 monosolvents (ethanol, n-propanol, isopropanol, n-butanol, acetone, acetonitrile, ethyl acetate, 1,4-dioxane, cyclohexane, 2-butanone, dimethyl sulfoxide (DMSO), and toluene) and the (ethanol + ethyl acetate) solvents system was determined using a static gravimetric method, with the following conditions: temperature is T = (283.15 to 323.15) K and pressure of p = 101.2 kPa. To sum up, the solubility of iohexol in ethanol was the highest, and the solubility in cyclohexane was the lowest. The order of the solubility of iohexol from high to low is ethanol (1.690 x 10(-3), 298.15 K) > n-propanol (1.041 x 10(-3), 298.15 K) > isopropanol (0.6738 x 10(-3), 298.15 K) > n-butanol (0.4159 x 10(-3), 298.15 K) > DMSO (0.3573 x 10(-3,) 298.15 > acetone (0.3082 x 10(-3), 298.15 > 2-butanone (0.2547 x 10(-3), 298.15 K) > ethyl acetate (0.2151 x 10(-3), 298.15 > acetonitrile (0.1463 x 10(-3), 298.15 K) > 1,4-dioxane (0.08301 x 10(-3), 298.15 > toluene (0.05118 x 10(-3), 298.15 K) > cyclohexane (0.01997 x 10(-3), 298.15 K). Two semiempirical models (modified Apelblat equation and 2h equation) served as the correlation equations to correlate the experimental solubility values of iohexol in different pure solvents. The Jouyban-Acree model, van't Hoff/Jouyban-Acree model, and Apelblat/Jouyban-Acree models served as the binary mixture system correlation equations. Compared with the correlation results, all the correlation models can fit the experimental solubility values of iohexol in pure or mixed solvent systems very well. Consequently, for the monosolvents, the relative average deviation (RAD) and root-mean-square deviation (RMSD) values did not exceed 1.66% and 2.42 X 10(-5), and the values are for the binary system are 0.66 X 10(-5) and 0.60%. Moreover, interactions of solute and solvents have been researched in 12 monosolvents. The hydrogen bonds and van der Waals interaction play an important role in the dissolution process of iohexol. Particularly, the experimental solubility values and correlation results of iohexol obtained play an important role in its purification, recrystallization, and formulation development in production.