Currently, industrial, automotive, and aerospace areas have a need for structural materials that can withstand oxidizing and aggressive environments at temperatures above 1000 0C. Mo-Si-B system intermetallics have been attracting attention as promising candidate materials for such applications, especially materials containing Mo5Si3 (T1) phase. However, Mo5Si3 single crystal has significant thermal expansion anisotropy along the a and c directions with α[Subscript C]/α[Subscript a]=2.2. Calculation by C. L. Fu et al. shows that this can result in substantially high residual thermal stresses, up to 1.8 Gpa, due to thermal expansion mismatch between different grains in the polycrystalline Mo5Si3 materials. These large stresses are higher than the compression and tension strength, so they can fracture weakly bonded grain boundaries in cooling processes during fabrication, cause grain boundary cracking. Reduction of this anisotropy of thermal expansion is necessary to produce a strain-free and crack-free microstructure. In this research, high temperature X-ray diffraction using synchrotron radiation in Debeye-Scherrer transmission geometry is employed to study the thermal expansion behavior of Mo-Si-B system intermetallics. Four multi-phase materials containing T1 phase with different compositions are explored in this study. High temperature X-ray diffraction experiment using synchrotron radiation is done at Advanced Photon Source (APS) of Argonne National Laboratory and Cornell High Energy Synchrotron Source (CHESS) of Cornell University. The Rietveld refinement of diffraction pattern is performed through using General Structure Analysis System (GSAS) program. All the Mo-Si-B intermetallics in this research show approximate linear thermal expansion behavior from room temperature up to around 10000C. For the Mo rich hyperstoichimoetric T1 phase, Mo replaces Si 4a site; their thermal expansion anisotropy tends to decrease with the increasing bonding distance of the 4b Mo-Mo atoms. For the Si rich hypostoichiometric T1 phase, the T1 phase is formed by Mo vacancy at 4b site, which helps to relief the anharmonicity of thermal expansion along c-direction and tends to decrease the thermal expansion anisotropy. Third generation synchrotron radiation coupled with an area detector has been shown to be an efficient and accurate way determining the coefficient of thermal expansion of materials with complex structure.