Hydrothermal diamond-anvil cell and Raman spectroscopy were used to measure the hydrogen isotope fractionation factor between gypsum and liquid water. Hydrogen isotopes of deuterium (D) and hydrogen (H) show the largest relative mass difference in all stable isotope systems. The exchange reaction between D and H would easily take place and the extent of exchange would be larger than others under same condition. So we selected the hydrogen isotopes for the investigation.The concept of fractionation factor is the quotient of ratios of heavy and light isotopes in different minerals, and can be expressed as αA-B＝RA/RB. There is a linear relationship between ratio of Raman peak intensities and ratio of corresponding amount of substances. So the fractionation factor between gypsum and heavy water can be expressed asα＝Ｉ(Ｄ－Ｏ)Ｉ(Ｈ－Ｏ)gypsumＩ(Ｄ－Ｏ)Ｉ(Ｈ－Ｏ)heavywaterThe experimental study for the isotope fractionation is based on the dissolution and recrystallization of minerals in aqueous solutions. The process can reach the total isotope fractionation equilibrium and get isotope fractionation factors with different temperatures. Compared with other methods, chemical synthesis one has following advantages: (1) short time for the experiment; (2) no problem about the equilibrium for isotope exchanges. It was proved that the new method would be more convenient and reliable for obtaining the isotopic fractionation factor compared with previous ways.