A water-soluble organic/niorganic hybrid nanodot based on polyhedral oligomeric silsesquioxane (POSS) and conjugated oligoelectrolyte is designed and synthesized for two-photon fluorescence imaging of cellular nucleus, which takes advantage of its small size (similar to 3.3 nm) that imparts nucleus permeability and substantial DNA-enhanced two-photon excited fluorescence that allows illuminating the nucleus with a high contrast.