The ring-opening reaction of phenolphthalein (PP) crystals under hydrostatic pressure provided by using a diamond anvil cell (DAC) is described in this paper for the first time. The color of the crystals changed into red from colorless visibly. The ring-opening threshold pressures could be adjusted by changing the substituent groups. Mechanochromic responses under hydrostatic pressure could also be achieved in polymer blends, which contributes to their practical applications.