This work attempts to introduce polyhedral oligomeric silsesquioxane compounds as a novel toughening agent for thermosetting systems. For this purpose, an acrylic/melamine thermosetting system was modified by OH-functional silsesquioxane nano-cage. Mechanical and thermo-mechanical behavior of resultant nanocomposites were studied by tensile and DMTA techniques. It was found that low content of silsesquioxane building blocks is sufficient to shift the mechanical behavior of the matrix from a brittle character to a flexible tough one. Various morphological techniques (SEM and TEM equipped with elemental analyzer together with XRD) were also utilized to clarify how nano-cages have been oriented within the matrix. It was revealed that nano-cages have been well dispersed in a molecular scale within the thermosetting network. The good dispersion of silsesquioxane compounds was assigned to the high compatibility within the matrix owing to their compact structure and OH-functional groups available on the cage.