A new liquid chromatography system in which tetrabutylammonium bromide semiclathrate hydrate (TBAB-SCH) was used as the column-packing material is proposed to evaluate the adsorption mechanisms of polar small molecules on a TBAB-SCH surface. It is revealed that the more hydrophilic molecules tend to be more strongly retained on the TBAB-SCH/hexane-diethyl ether interface and the retentions of aromatics (ARs) and crown ethers (CEs) are differently controlled. CEs are likely retained on the TBAB-SCH interface via hydrogen-bond formation as well on water-ice, whereas the retention mechanism of ARs is unique to TBAB-SCH and has not previously been observed on water-ice. This difference between CEs and ARs may arise from differences in the types of polar groups or molecular size.This chromatographic approach will provide useful knowledge for evaluating the adsorption mechanisms of inhibitors for clathrate hydrate agglomeration, which is a common agglomeration problem experienced by industries.