Tautomeric equilibria of 2-pyridone (PD) and 2-hydroxypyridine (HP) dimeric forms as well as PD/HP complexes mediated by the conjugated dual hydrogen-bonding (CDHB) formation have been studied by ab initio molecular orbital calculations up to the 6-31+G** basis set at the Moller-Plesset level. The result in combination with the semiempirical solvation free-energy calculation reasonably predicts the relative free energy and consequently the tautomeric equilibria between PD, HP, their corresponding dimers and PD/HP complex in the gas phase as well as in solution. The results also indicate that the strength of dual hydrogen bonding resonantly affects the PD and HP electronic structures upon CDHB formation, resulting in an additional stabilization energy. Further calculation shows that the tautomeric equilibria can be fine-tuned by the formation of a hydrogen-bonded complex with guest molecules possessing bifunctional hydrogen bonds. The results lead to a possible mechanism suggesting that the tautomerization of a specific DNA base may be induced by forming a complex with an intruder, i.e., a specific molecule with multiple hydrogen-bonding capability, which triggers the mutation process.