A novel selective separation method for organic compounds, especially thermosensitive substances, has been proposed using unsubstituted beta-cyclodextrin (beta-CD) as a host and some alcohols and aldehydes as model guests in aqueous solution. The separation factors were evaluated from the extraction of an equimolar mixture of alcohol and aldehyde compounds. The inclusion equilibrium constants for several alcohols and aldehydes over beta-CD have been calculated through their UV-vis spectra. The Gibbs free energy changes of beta-CD/substrates complexes (Delta G) have been calculated combined B3LYP/6-31G(d)//ONIOM2(B3LYP/6-31G(d):PM3) with semicontinuum solvation model. The difference of Gibbs free energy changes (Delta Delta G) for the inclusion complexes formed via the intermolecular weak interactions e.g., hydrogen bond and electrostatic interaction was the reason why alcohol and aldehyde compounds could be selectively separated. (C) 2010 American Institute of Chemical Engineers AIChE J, 57: 2341-2352, 2011