Organic-inorganic hybrid materials, prepared via chemical synthesis route or physical blending of functionalized nanofillers within polymer matrix, have gained an increased attention in the recent years. Polyhedral oligomeric silsesquioxane (POSS) nanoparticles, due to their nanometer size and functionalization possibilities, are applied as effective modifiersboth chemical and physical, for polymer matrices, including polyurethanes (PU). In this work, we describe the synthesis and processing of polyurethane/POSS hybrid nanocomposites and discuss the influence of POSS moieties on the thermal properties of PU matrices. Glass transition, the crystallinity of the soft phase, as well as the order-disorder transitions are affected by the incorporation of POSS in the polyurethane structure. Direct polymer-POSS interaction, or -indirect-due to the suppression or enhancement of microphase separation by the POSS moieties are discussed in terms of topology of the polymeric structure with the key role of POSS functionalization.