The solubility of a blowing agent in a polyol plays an important role in determining the overall quality of the polyurethane foam. For many years, concerns have been raised about the high ozone depleting potential (ODP) of traditionally used blowing agents such as chlorofluorocarbons and hydrochlorofluorocarbons. To this end, hydrofluorocarbons (HFCs) have been identified to be long-term replacements as the future blowing agents. In this study, we chose four HFCs, namely, HFC-125 (1,1,1,2,2-pentafluoroethane), HFC-152a (1,1-difluoroethane), HFC-143a (1,1,1-trifluoroethane), and HFC-32 (difluoromethane), and measured their solubilities in three polyols, namely, Pluracol 975, Pluracol 355, and Terol 352, using a degassed vapor pressure apparatus. Results indicate that there is a prominent effect of the structure of the blowing agent molecule and the functionality of the polyol on the solubility. HFC152a showed good solubility in Pluracol 975 and Pluracol 355, whereas all blowing agents showed limited solubility in Terol 352. In general, the least soluble blowing agent was HFC-143a. The experimental results have been correlated with the Sanchez-Lacombe equation of state, which was able to describe the polyol + blowing agent systems well.