The Ti-3.6Al-5.2Mo-4.6Cr-4.7 V-0.7Fe (Ti-351) alloy was developed based on the d-electron theory and the β grain growth behavior during isothermal heat treatment (IHT) was investigated. The nanoindentation analysis of β grain and the tensile properties with different IHT states were carried out. The results showed the grain coarsening temperature of Ti-351 alloy is 850 °C. The grain growth activation energy Q of 75.11–133.92 kJ/mol and the grain growth exponents n of 0.28–0.33 were calculated, indicating a competition between alloy atom diffusion and grain boundary migration. Due to the enhanced diffusion of solute atoms and lower substructure density at higher IHT temperature and longer holding time, the hardness and creep stiffness of β grain would decrease as indicated by nanoindentation test, while the total work W and the plastic deformation work Wp would increase, suggesting an improved toughness of the alloy. In order to achieve full recrystallization of β grains and a better balance between tensile strength and plasticity at room temperature, it is recommended to select a solution heat treatment regime at 850–900 ℃ for 2–4 h.