Molecular conformation is closely related to its luminescence process, and pressure is one of the effective tools to regulate molecular conformation. In this letter, we studied the evolution of salicylic acid crystal fluorescence under high pressure and obtained enhanced emission during the compression. At 0–4 GPa, the rotamerization process led to the energy dissipation, which resulted in the fluorescence quenching. After 4 GPa, the rotamerization process completed. The excited-state intramolecular proton transfer (ESIPT) process of SA was inhibited, and due to the strengthened intermolecular hydrogen bond, the non-radiative decay reduced, which resulted in emission enhancement. This work reveals the impact of hydrogen bond and molecular conformation on luminescence and ideas for the development of new small-molecule luminescent materials are furnished.