The interface adhesion properties are crucial for designing and fabricating two-dimensional materials and related nanoelectronic and nanomechanical devices. Although some progress of the interface adhesion properties of two-dimensional materials has been made, the underlying mechanism behind the size and temperature dependence of interface adhesion energy and related physical properties from the perspective of atomistic origin remain unclear. In this work, we investigate the effects of size and temperature on the thermal expansion coefficient and Young’s modulus of MoS ₂as well as interface adhesion energy of MoS ₂/SiO ₂based on the atomic-bond-relaxation approach and continuum medium mechanics. It is found that the thermal expansion coefficient of monolayer MoS ₂is significantly larger than that of its few-layer and bulk counterparts under the condition of ambient temperature due to size effect and its influence on Debye temperature, whereas the thermal expansion coefficient increases with temperature going up and almost tends to a constant as the temperature approaches the Debye temperature. Moreover, the variations of bond identity induced by size effect and temperature effect will change the mechanical properties of MoS ₂. When the temperature is fixed, the Young’s modulus of MoS ₂increases with size decreasing. However, the thermal strain induces the volume expansion, resulting in the Young’s modulus of MoS ₂decreasing. Furthermore, the size and temperature dependence of lattice strain, mismatch strain of interface, and Young’s modulus will lead the van der Waals interaction energy and elastic strain energy to change, resulting in the change of interface adhesion energy of MoS ₂/SiO ₂. Noticeably, the interface adhesion energy of MoS ₂/SiO ₂gradually increases with MoS ₂size decreasing, while the thermal strain induced by temperature causes interface adhesion energy of MoS ₂/SiO ₂to decrease with temperature increasing. In addition, we predict the conditions of the interface separation of MoS ₂/SiO ₂under different sizes and temperatures. Our results demonstrate that increasing both size and temperature can significantly reduce the interface adhesion energy, which is of great benefit in detaching MoS ₂film from the substrate. Therefore, the proposed theory not only clarifies the physical mechanism regarding the interface adhesion properties of transition metal dichalcogenides (TMDs) membranes, but also provides an effective way to design TMDs-based nanodevices for desirable applications.