As an essential precondition of ore-forming process in the hydrothermal system, water-rock interaction is not only an important subject of metallogeny but also an international geological trend. This process is along with isotopic exchange, which changes the isotopic compositions of fluid and rock. As tracers of non-traditional stable isotopes, boron and lithium isotopes are often used to constrain fluid-basalt hydrothermal interaction process. This paper gives a detailed review of factors of boron and lithium isotopic fractionation variation, which include temperature, pH values, primary phase dissolution, surface exchange and secondary mineral formation. Some conclusions have been reached:① Generally, the fluids in equilibrium become more quickly enriched in ¹¹B and end with higher δ¹¹B; At low temperatures (<150℃) Li is taken into secondary minerals and at high temperatures (>200℃) it is leached from the rocks. ② Primary phase dissolution and surface exchange hardly have influence upon lithium isotope fractionation. ③ Usually, the heavier isotope ⁷Li preferentially goes into solution and finally the solution tends to be with higher δ⁷Li. Simulation of mass balance equilibrium of the evolution of isotopic compositions in the fluid and the bulk rock with the reaction progress was also made in this paper.