The asymmetric reduction of acetophenone with sodium borohydride in the presence of β-cyclodextrin (β-CD) as catalyst can improve selectivity and yield. The interaction between acetophenone and β-CD plays an important role for the reduction of acetophenone. This work studies the reaction of acetophenone in the presence of β-CD using density functional theory (DFT) method. Energy is investigated to find out the lowest energy of two possible complexation models. The geometrical structure confirms that acetophenone inserts into the cavity mainly from the secondary hydroxyl side. Hydrogen bonds are researched on the basis of natural bonding orbital (NBO) analysis, the results confirm the donor-acceptor interactions of complex. Mülliken charge and frontier orbital are employed for revealing the electronic transfer. In addition, (13)C nuclear magnetic resonance ((13)CNMR) spectroscopy shows that the active site concentrates on the carbon atom of carbonyl group. The probable catalytic mechanism of β-CD is discussed in terms of the calculated parameters.