Pandat software based on Calculations of phase diagram (CALPHAD) was used in this study. Six binary systems and four ternary systems in the Ti-Al-Fe-V system were evaluated, compared, and optimized. A thermodynamic database of Ti-Al-Fe-V titanium alloys was established by selecting the most recent, accurate, and self-consistent thermodynamic parameters. The database was used to simulate the organization of equilibrium solidification and non-equilibrium solidification alloys of Ti-10V-2Fe-3Al, Ti-10V-3Al-1Fe and Ti-10V-3Al. The precipitated phase fractions of Ti-10V-2Fe-3Al at different temperatures were calculated using the database. The effect of different Fe contents and aging temperatures on the phase composition of the Ti-10V-2Fe-3Al alloy is given in conjunction with the calculated results. There is good agreement with the experimental results for the heat treatment regimens given by the calculations. The above results show that thermodynamic calculations based on phase diagrams can guide the formulation of process parameters for alloy casting and heat treatment. The established thermodynamic database for Ti-Al-Fe-V titanium alloys is accurate and reliable.