Isothermal compression tests were conducted at Thermecmaster-Z simulator, and grain size of the prior a phase was measured at a Leica LABOR-LUX12MFS/ST microscope for quantitative metallography. A methodology to establish a constitutive equation with grain size was proposed with the help of the experimental results. Combining FEM and the present constitutive equation at high temperature deformation, grain size of the prior alpha phase was simulated during the isothermal forging of a TC6 titanium alloy disc. The present results illustrate grain size and distribution of the prior a phase in the forging process of TC6 titanium alloy disc in detail. The maximum difference between the calculated results and the experimental is not more than 15%.