The novel photodeamination process of cresol derivatives 1 and 3 has been reported experimentally (j. Org. Chem. 2015, 80, 10817). However, a full theoretical interpretation of the mechanism is still lacking. In the present study, we aim to provide insight into the factors that promote the deamination reaction through density functional theory (DFT) and time dependent OFT methods. Calculated absorption and emission spectra arc in good agreement with the experimental results. Hydrogen-bond strengthening in the excited state has been verified by analyzing relevant bond parameters and vibrational frequencies as well as frontier molecular orbitals (FMOs), implying that hydrogen-bond interaction acts as the important parameter for the excited-state intramolecular proton-transfer (ESIPT) reaction. The proton-transfer and deamination reactions have been qualitatively analyzed through Gibbs free-energy reaction profiles in different electronic states. It can be concluded that the ESIPT and photodeamination reactions occur in the excited state. To further illustrate the photodeamination mechanism, the constructed 2D potential-energy surface indicates that the photodeamination reaction is infeasible without the ESIPT reaction. This work provides the first theoretical rationale for ESIPT-induced photodeamination occurring spontaneously because of protonation of a basic nitrogen atom.