Supercritical carbon dioxide (ScCO2) plays an important role in industries, such as in the purification/crystallization processes in the pharmaceutical industry, in the extraction of natural flavors and nutrients in the food/pharmaceutical industry, and in wafer cleaning in the semiconductor industry. Therefore, the solubility of solid solutes in ScCO2, with and without organic solvents, is essential information for the design and optimization of such processes. It has been shown that PR+COSMOSAC EOS is able to provide a reasonable prediction accuracy for drug solubility in organic solvents and in ScCO2. In this study, PR+COSMOSAC EOS is applied to predict the solubility of solid solutes in mixtures of ScCO2 + organic solvents (e.g., acetone and ethanol). The solubility of 23 solid solutes in different mixtures of ScCO2 + organic solvents with pressures up to 40 MPa and temperatures ranging from 298.15 K to 353.15 K are used to evaluate the accuracy of PR+COSMOSAC EOS. The overall average logarithmic deviation (ALD-x) in the prediction of drug solubility in binary ScCO2 + organic solvent mixtures is 0.76. The accuracy is slightly better than that of the drug solubility in pure ScCO2 and similar to that in pure organic solvents. This study shows that PR+COSMOSAC EOS may be a useful tool in predicting the solubility of solid solutes when no experimental data are available.