The MnO-SiO2-TiO2-Ti2O3 system is a key oxide system for well known “Oxide Metallurgy” for HSLA steel. However, the available thermodynamic data for this system are rare and even the available experimental data are often inconsistent with each other. In the present study, experimental and thermodynamic modeling studies have been carried out on the MnO-SiO2-TiO2-Ti2O3 system. High-temperature equilibration and quenching technique followed by EPMA (electron probe X-ray microanalysis) was used to determine liquidus temperatures and solid solubilities of the crystalline phases such as manganosite, rutile, spinel, pyrophanite, pseudobrookite, tridymite, etc. in the temperature range from 1200°C to 1550°C (1473 to 1823 K) under an atmosphere controlled by CO-CO2 gas mixture. These equilibrium data for the MnO-SiO2-TiO2-Ti2O3 system, combined with previously reported data for this system, were used to obtain an self-consistent set of optimized parameters of thermodynamic models for all phases. In addition, the application of the optimized thermodynamic database to oxide metallurgy was discussed.