Brucite [Mg(OH)2] has been extensively studied as a simple yet important analog for studying physical and chemical properties of hydrous minerals, and fluorine substitution (OH– = F–) is common in hydrous minerals since the radius of F– is similar to that of O2−. We synthesized two F-bearing brucite samples, Mg(OH)1.78F0.22 and Mg(OH)1.16F0.84, at 9.5 GPa and 1373 K. Single-crystal X-ray diffraction measurements indicate that both phases still crystallize in the space group of P3m1, and fluorine substitution significantly reduces the unit-cell volume, axial lengths, and averaged Mg-O(F) bond lengths. The averaged O···H distances get slightly shortened, and the H-O-H angles become smaller due to the fluorine effect. Additional IR-active OH-stretching bands are observed at 3660, 3644, and 3513 cm−1 for the F-bearing samples, besides the original one at 3695 cm−1. In situ high-temperature and high-pressure Raman and Fourier transform infrared (FTIR) spectra were collected on the F-bearing brucite samples, and comparisons were made with the natural one with 0.7 mol% F–. The temperature dependence [(∂vi/∂T)P] of the OH-stretching modes is inversely correlated to the vibrational frequencies from 3500 to 3700 cm−1, whereas (∂vi/∂P)T is in positive correlation with vi. In addition, the dehydration temperatures of the F-bearing brucites are 100–150 K higher than that for the F-free sample at ambient pressure. By creating new proton positions in lower energies, fluorine substitution stabilizes hydrous minerals (like brucite) to higher temperatures and significantly affects their thermodynamic properties, which has significant implications in mineral physical and geochemical studies.