The distinct piezochromic luminescent responses of chargeÀtransfer inclusion crystals, which consist of small aromatic guest molecules with naphthalenediimide derivatives, are reported. Reversible multichromism is observed over the entire visible region in response to high pressure, whereas a weak response to mechanical grinding is evident. High-pressure single-crystal X-ray diffraction analysis and TD-DFT calculations clearly suggest that high compression induces a closer arrangement with a short interfacial distance between small aromatic guest molecules and naphthalenediimide derivatives, which is proposed as the origin of the drastic luminescent color change.The development of luminescent molecules that are sensitive to external stimuli has attracted considerable attention in recent years owing to their potential applications, such as in bioimaging, display, memory, and sensors. [1,2] Materials sensitive to external stimuli, such as pH, light, and temperature, have been relatively well investigated, whereas piezochromic luminescent materials, which change their luminescence upon mechanical grinding/shearing or high compression, remain poorly understood. Indeed, a number of mechanochromic systems, based on organic molecules [3] and metal complexes, [4] have been developed. In early stages of research, high-pressure effects on the electrostatic structure of organic crystals such as anthracene, chrysene, and pyrene were reported. [5] Based on the recent advance in understanding the mechanochromic systems, Zou, Tian and co-workers have reported anthracenederivatives, which exhibit mechanochromism after mechanical grinding and high pressure. [3a] In 2013, Saito, Yamaguchi and co-workers reported a propeller-shaped tetrathiazoylthiophene whose luminescence displayed distinct emission color changes in response to mechanical grinding and high pressure. [3c] Intramolecular charge-transfer (CT) fluorophores with an electron acceptor (A) and an electron donor (D) were used to demonstrate photoluminescence color changes in response to mechanical grinding and high pressure. In the molecular designs, intramolecular rotation of phenyl rings and packing modes, such as p-p stacked aggregates or amorphous states, are essential to tune the emission properties. However, the organic molecules that have been reported so far possess a major drawback. Most of the organic molecules that exhibit mechanochromism show the change of molecular packing modes and molecular torsion angles based on monomer emission, excimer emission, and intramolecular CT emission. Therefore, when grinding or smashing to make the crystal smaller, the crystal structure unexpectedly changes or collapses to form an amorphous powder. It is necessary to use pristine crystals when evaluating the piezochromic properties against high pressure. To the best of our knowledge, organic molecules that show a weak fluorescence response to mechanical grinding/smashing (anisotropic pressure) but significant response to high pressure (quasi-isotropic pressure) are rare.A...