Reaction field calculation combined with the AM1 molecular orbital method is applied in order to understand why intermolecular hydrogen bonding is stabilized at the lipid-water interface. Here, we focus on the interaction between a guanidinium-functionalized lipid (1) and phosphate and between a diaminotriazine-functionalized lipid (2) and thymine. The interface is approximated by a double layer composed of two dielectrics. The lower dielectric medium with a dielectric constant of 2 corresponds to the lipid layer, and the higher dielectric medium with dielectric constant of 80 to the aqueous subphase. A pair of interacting molecules is placed on/near the interface, and the binding energy profile is obtained. For comparison, the calculation of binding energy is also performed for a homogeneous system defined as a single dielectric constant, corresponding to a normal solution system. It is shown that the calculation reproduces well the observed binding constants, when the position of the interface is appropriately displaced relative to the interacting molecules. One of the most important findings is that hydrogen bonding is remarkably strengthened even if the binding site is exposed to the aqueous subphase. The results for the binding profiles are interpreted from those for Mulliken population analysis.