We studied interfacial reactions in Co/amorphous Si(a-Si) multilayers by transmission electron microscopy. We found that an intermixed layer of amorphous cobalt silicide formed in the as-deposited state. To explain the solid-state amorphization reaction, two parameters were used. They were the thermodynamic driving force (heat of formation) and the interfacial energy. The initial amorphization reaction in Co/a-Si multilayers was thermodynamically and kinetically favored. However, the formed amorphous interlayer remained about 1 nm thick and did not grow thicker with increasing modulation period and annealing temperature. The reason for this phenomenon was that the amorphous interlayer acted as a diffusion barrier to impede the amorphization reaction in Co/a-Si multilayers. Co2Si phase was always the preferred phase in the crystallization process for different average compositions of the multilayers. The mechanism that controlled the phase selection in Co/a-Si interfacial reaction was interpreted by using the model of modified heat of formation.