The host–guest interaction is necessary for the stabilization of hydrates. Using Density Function Theory methods, the host–guest interaction within an unconventional chlorine hydrate was investigated, in combination with typical noncovalent analyses. The host–guest interaction energy was predicted to be as high as 17.51 kcal/mol, which was stronger than the typical van der Waals (vdW) interaction, due to an involvement of up to 20 Cl…O interactions. Polarization and dispersion energies made up the main contribution to the total interaction energy. Further visualization of the host–guest interaction validated, together with the general Cl…O interaction, another vdW interaction between the guest-Cl atom and the five-membered H2O cluster. Isosurfaces associated with two patterns of vdW interactions yielded a better “fit” in shape, suggesting their cooperativity in stabilizing the steric configuration. The σ-region on the guest-Cl atom was verified to regulate the electron redistribution over the molecular space. These results are useful for understanding specific halogen behavior, and the origin and nature of host–guest interaction in hydrates. © 2013 Wiley Periodicals, Inc.