We have designed and synthesized a pair of sequence isomeric giant surfactants based on polystyrene (PS) and polyhedral oligomeric silsesquioxane (POSS) nanoparticles. Although these two macromolecules possess identical compositions as "sequence isomers", the distinctly arranged POSS sequences lead to different molecular packing conformations, and further induce distinguished self-assembly behaviors in DMF/water solutions.