A corresponding relationship was established between grain structure evolution, extrusion simulation and profile fabrication, and the grain structure was optimized for extrusion profile with typical section of 2196 Al-Li alloy. The results show that the alloy exhibits excellent hot deformability at a relative wide parameters range. The dominate mechanism of microstructure evolution is dynamic recovery, although some localized dynamic recrystallization is also observed, caused by strain concentration under a couple of lower temperature (350℃, 400℃) and higher strain rate of 10 s_-1^. Compared to experimental compression deformation, the larger strain promotes dynamic recrystalliztion during extrusion process, and the differences of deformation conditions on profile section lead to non-homogeneous grain structure. Based on the equipment capability, a deformation condition that temperature 430~440℃ and strain rate of 0.005~0.95s_-1 ^{on profile section} is suggested to obtain relatively uniform microstructure, the lower fraction of recrystallization and abundant sub-grain structure, which is benefit for the strength and toughness matching.