In the present study, the Sanchez-Lacombe equation of state (i.e., SL EOS) was employed to calculate the solubilities of alpha-olefins in polyolefins over a wide range of pressures and temperatures. The characteristic parameters ( i.e., P*, T*, and rho*) of the pure components, appearing in the Sanchez-Lacombe EOS, were estimated using a molecular dynamic procedure (MD). For all binary systems examined, a single binary parameter, k(ij), accounting for the interactions between the penetrant molecules and the polymer chains was used to fit model predictions to available solubility measurements. The value of the binary interaction parameter was found to depend on the type of the penetrant molecules, the comonomer type in the ethylene copolymers, and the polymer crystallinity as well as the selected experimental conditions (i.e., temperature and pressure). The theoretically calculated solubilities were found to be in excellent agreement with the corresponding experimentally measured values, demonstrating the capability of the SL EOS to predict the solubility of alpha-olefins in semicrystalline polyolefins.