The room-temperature deformation behavior of single crystals of transition-metal (TM) disilicides with the tetragonal C11_b (TM=Mo) and hexagonal C40 (TM = V, Cr, Nb and Ta) structures has been investigated by micropillar compression as a function of specimen size, paying special attention to the deformation behavior of the equivalent slip ({110}<1¯11> and (0001)<21¯1¯0>, respectively for the two structures). In contrast to bulk single crystals, in which high temperature at least exceeding 400 °C is usually needed for the operation of the equivalent slip, plastic flow is observed by the operation of the equivalent slip at room temperature for all these TM disilicides in the micropillar form. The critical resolved shear stress (CRSS) value exhibits the ‘smaller is stronger’ behavior following an inverse power-law relationship for all these TM disilicides. The bulk CRSS values at room temperature estimated from the specimen size dependence are 620 ± 40, 240 ± 20, 1,440 ± 10, 640 ± 20 and 1,300 ± 30 MPa for MoSi₂, VSi₂, CrSi₂, NbSi₂ and TaSi₂, respectively. Transmission electron microscopy reveals that the equivalent slip at room temperature occurs by a conventional shear mechanism for all TM disilicides, indicating the change in deformation mechanism from synchroshear in bulk to conventional shear in micropillars occurs in CrSi₂ with decreasing temperature.