In this paper the effect of isothermal forging process parameters on the microstructure and the mechanical properties of Ti-5Al-5Mo-5V-1Cr-1Fe titanium alloy was researched. The results of the tests indicate that, in the temperature range of 755~905 °C and the deformation degree range of 20~60 %, with the increase of deforming temperature, the volume of primary α-phases decrease, but the globularization extent of the α-phases increases and partial secondary α-phases transform into equiaxed shape. At the temperature of 860 °C, the alloy exhibits excellent strength and plasticity, as the uniform and fine duplex microstructure formed after isothermal forging. When the deformation degree increased from 20% to 60%, primary and secondary α-phases were gradually broken and the recrystallization energy was continually accumulated, which ceaselessly strengthened the properties of the alloy. With the increase of forging times, the globularization extent of decreases, leaving the chain of α-phases, which damages the strength and plasticity of the alloy.