The molecular crystals of acridonyl-tetraphenylethene (AD-TPE) exhibit an intriguing turn-on and color-tuned luminescence in response to mechanical grinding and hydrostatic compression. On the basis of in-depth experimental and computational studies, it is hypothesized that the origin of the piezochromic behavior from the D-phase to the B-phase is the change of the intramolecular geometrical conformation, especially for the torsion angle between the TPE and AD moiety. The different molecular conformation in the two distinctive solid phases causes the substantial switching of the intramolecular charge transfer (ICT) process, which can be directly correlated with the subsequent fluorescence from locally excited (LE) state and ICT state in both phases. The AD-TPE molecular system presents a very rare example of high-contrast reversible fluorescence tuning driven by a switching of the excited state in the solid state under the mechanical stimuli, and thus provides a novel mechanism of the piezochromic behavior.