The feasibility of controlling the selective precipitation of pancreatic proteins was investigated using designed organic antisolvents in a drowning-out process. First, the solubility of pancreatin was measured in water-organic solutions when the organic species and their composition in the solution were varied. Due to the hydrophilicity of the proteins, solubility was rapidly reduced when the organic species fraction in the solution was increased. This reduced solubility was further amplified with a less polar organic species. Plus, the pancreatin solubility as a predictor was found to agree well with the solution polarity as a single parameter, expressed in terms of the Hildebrand solubility parameter. The precipitation of pancreatin was then carried out with various antisolvents composed of alcoholic and nonalcoholic species. The precipitation was promoted along with an antisolvent of a lower polarity, which was also functionally related to the solution polarity. The amylase, lipase, and protease proteins contained in the pancreatin displayed different precipitation behaviors depending on the polarity of the antisolvent. Thus, it was possible to selectively separate the proteins and control their composition in the precipitated pancreatin.