Electron–phonon (e–p) polar-coupling interactions in C12H17ClN4OS·HCl·H2O crystals exhibiting an upward frequency shift with increasing temperature are investigated using terahertz and far-infrared spectroscopies, and the structural condition required for effective e–p polar-coupling interactions in crystals are uncovered. X-ray crystallography and first-principles calculations reveal that the key structure for the e−p polar-coupling interaction is an open cavity near the considered vibration. Based on the temperature-dependent frequency shift proportional to the Bose−Einstein statistical factor, the interaction strength and characteristic frequency of phonons interacting with electrons are determined at 5.3 × 10–3 cm–1 K–1 and 76.6 cm–1, respectively. From the phonon dispersion curves exhibiting LO (longitudinal optical)–TO (transverse optical) splitting, we find that the highest frequency LO phonon participates in the polar-coupling interaction.