Hydrogen bond (HB) is of an important factor on theory. In this work, the effect of a solvent on the performance of a newly synthesized fluorescent probe for detecting endogenous ONOO- is studied by using four different solvent models, noted as polarizable continuum model (PCM), ONIOM, HB, and HB + PCM models, respectively, where HB contribution is thus given special attention. The theoretical results show that the absorption and emission properties of the probe are obviously influenced by the HB; for example, the HB + PCM model including both short- and long-range interactions between the solute and solvent molecules gives the exact description on the solvent effect. In particular, the responsive mechanism of the probe for sensing ONOO- is explored by analyzing the charge variations between the excited states and ground states of the free molecules and their reaction products. It is demonstrated that the mechanism is attributed to an intramolecular charge transfer, where the HB has an important contribution. Moreover, the influence of HB on a two-photon absorption cross section has been considered. Our investigation reveals that the HB has an important influence on the optical properties and responsive mechanism of the fluorescent probe, and it must be considered for theoretical calculations.