CuSiO₂ catalysts were prepared by homogeneous deposition–precipitation with a wide range of Cu contents (8.8–100 wt%) and Cu particle sizes (2.1–111.1 nm). These catalysts were evaluated in the selective hydrogenolysis of biomass-derived xylitol to ethylene glycol and propylene glycol under the promotion of Ca(OH)₂ base. Their catalytic activity and selectivity to the two glycols depended strongly on the Cu particle sizes, which increased with the particle sizes and reached the maximum values at around 20–35 nm. Such size effects are apparently attributed to the effects on the dehydrogenation and hydrogenation activities of the Cu catalysts, and consequently on the xylitol hydrogenolysis pathways, reflecting the structural requirement for the xylitol hydrogenolysis. The effects of the reaction parameters including H₂ pressure (0–8.0 MPa), temperature (433–493 K) and pH values (7.0–12.4, adjusted by changing the amount of Ca(OH)₂) were examined. These effects confirmed the reaction pathways previously proposed for the xylitol hydrogenolysis to the two glycols, involving the dehydrogenation of xylitol to xylose on Cu as the rate-determining step, followed by the retro-aldol condensation of xylose with Ca(OH)₂ to glycolaldehyde and glyceraldehyde, and their subsequent hydrogenation to ultimately form glycols in competition with their side reactions to glycolic acid and lactic acid in the presence of Ca(OH)₂. Upon optimizing the reaction conditions (473 K, 6.0 MPa H₂ and sufficient Ca(OH)₂), nearly 100% xylitol conversion and 54.4% combined selectivity to ethylene glycol and propylene glycol were obtained on CuSiO₂ with Cu size of 35.7 nm, comparable to those on the previously reported Ni- and Ru- based catalysts. Clearly, this study provides directions for the design of more efficient Cu catalysts and the optimization of the reaction parameters toward the efficient polyol hydrogenolysis into glycols.