A significant number of landslides occur in cold regions because of freezing and thawing cycles. The instability of thawing slopes can cause serious damage to transportation infrastructure and property, and even loss of human life. This type of landslide is difficult to analyze by the traditional limit-equilibrium methods, however, because of the complicated multi-physics processes involved. This paper describes a holistic microstructure-based random finite element model (RFEM) to simulate the stability of a thawing slope. The RFEM model is developed to simulate the bulk behaviors of frozen and unfrozen soils based on the behaviors of individual phases. The phase coded image of a frozen silty clay is first custom built and then converted into a finite element model. The mechanical behaviors of individual phases of the frozen soil are calibrated by uniaxial compressive test. The triaxial test is then simulated by RFEM to obtain the shear strength parameters of frozen and unfrozen soils. Coupled thermal-mechanical REFM models are developed to simulate the effects of temperature on the displacement field and stress field in the slope. From the results, the local factor of safety field can be determined. The development of local factor of safety and potential failure surface associated with the thawing process over a typical year are simulated by this new model. The variations in the stability of thawing slopes predicted by this model are consistent with field observations as well as the global-wise slope stability analysis.