A novel synthesis process and characterization of nano-Calcium fluoride(n-CaF2) single crystal prepared from phosphogypsum waste. The phosphogypsum (CaSO4,•2H2O) powder has been mechanically mixed with NH4F in presence of a controlled amount of water. The mixture still sintered for 48 hours until the formation of nano Calcium fluoride particles. The n-CaF2 particles have been characterized by several techniques, The techniques utilized included X-ray diffraction (XRD), infrared spectroscopy (IR), and scanning electron microscopy (SEM).Therefore, it was confirmed that very pure n-CaF2 was obtained with a Ca / F ratio of 0.5 and an average crystalizing size measured according to the Debye-Scherrer equation of 11 nm. Based on the findings reached, The characterization data revealed successful synthesis of n-CaF2 from phosphogypsum. Additionally, the adsorption performance of the elaborated n-CaF2 was tested in Reactive Blue 21 (RB21) anionic dye removal, Adsorption tests were conducted in a batch reactor, focusing on key factors such as contact time, which can significantly influence the adsorption results. adsorption amount, pH, and dye concentration were tested. Hence results show an important adsorption performance of n-CaF2 with Reactive Blue 21 removal rate up to 90%.