A novel luminescent polyhedral oligomeric silsesquioxane (POSS) containing in the structure a fluorescein derivative molecule and a carboxylic functionality, suitable to anchor different organic compounds (dyes, markers, drugs, contrast agents, …), was successfully synthesized and characterized in this manuscript by a multidisciplinary approach. An emission enhancement of the dye of ca. four times was found after reaction with POSS, rendering this new hybrid compound a promising contrast agent for optical imaging. In vitro tests on tumoral HeLa cells demonstrated that the luminescent POSS (namely POSS_F), here described, is able to be taken up in the cell cytosol by an efficient and selective process. Its high chemical versatility and peculiar properties could render this novel bifunctional POSS a molecular platform for biomedical applications.