Herein an able, facile, coherent, and environmentally benign synthesis of the C–O coupling reaction based on the functionalized mesoporous silica SBA-16 (Co^II immobilized on mesoporous SBA-16 functionalized by aminated 3-glycidyloxypropyltrimethoxysilane with aminoguanidine nitrate), is described. The mesostructured nanocatalyst (SBA-16/GPTMS-NH₂–Co^II) is characterized by various analytical techniques such as FT-IR, small-angle XRD, XRD, BET, TEM, FE-SEM, EDX, EDX-mapping, and ICP-OES analysis. Cage-like mesoporous SBA-16 efficiently managed dispersed the metal and organic species in the well-ordered siliceous frameworks. It was found that the aforementioned mesostructured catalyst with a special structure and particle size distribution (3–8 nm) displayed great catalytic performance to promote of the C–O cross-coupling reaction from the iodobenzene and phenol in solvent-free conditions. Plus, SBA-16/GPTMS-NH₂–Co^II as an inimitable heterogeneous nanocatalyst can be readily separated from the reaction mixture by simple filtration under reaction conditions and recycled at least five times without any loss of its catalytic efficiency.