The ground-state intramolecular double proton transfer process of 2-(2,5-dihydroxyphenyl)-4(3H)-quinazolinone (DHPQ) and DHPQ@CB7 was studied systematically at the B3LYP/6-311++G(d) and ONIOM(B3LYP/6-311 ++G(d): PM3) levels. The structures and energies of all isomers for DHPQ and the transition states in the double proton transfer paths were determined. Through analysising the changes of structures and the differences of energy, the double proton transfer mechanism was explared existed in DHPQ, nanometer cage effect was considered on the thermodynamic properties in the process, at the same time, geometric matching relation between the nanocavity and DHPQ was studied as well as the effect of H2O medium on DHPQ proton transfer process. The results showed that double proton transfer process in DHPQ carried out step by step, the limit of nano cavity produced a large energy barrier, inhibiting the intramolecular proton transfer process, and the introduction of water solvent promoted the path 2 but inhibited path 1.