The kinetics and phase evolution of silicide formation at the Ni0.8Mo0.2/Si interface in multilayer thin-film systems were systematically studied depending on ration of layer thicknesses and annealing temperature (300°C–600°C). Complementary analytical techniques, such as X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), X-ray reflectometry (XRR), transmission electron microscopy (TEM, including high-resolution) and selected area electron diffraction (SAED) were used to obtain both surface and bulk structural and chemical composition properties. It was established that the initial stoichiometry of the formed silicides is a combination of nickel-enriched Ni3Si, Ni31Si12 and Ni2Si compounds. When the proportion of the Si layer is greater relative to the Ni0.8Mo0.2 layer, the formation of additional NiSi compound was traced. Annealing of multilayer systems leads to a redistribution of phases: the proportion of Si-enriched phases (NiSi and NiSi2) increases while the proportion of Ni-enriched phases decreases. The crystallization temperature of the multilayer structure is determined by the ratio of the thicknesses of the main layers: the greater the thickness of the silicon layer, the higher the temperature at which crystallization occurs. Multilayer structure with highest Si content remains amorphous and retain their layering during annealing up to a temperature of 450°C.