A novel aggregation- and crystallization-induced emission luminophore (ENPOMe) containing tetraphenylethene and acrylonitrile moieties with high fluorescence efficiency (Φ(F) of up to 0.85) has been easily synthesized. ENPOMe has an exceptionally large two-photon absorption cross section (σ) of 5548 GM, and exhibits striking multi-stimuli-responsive single- and two-photon fluorescence switching with excellent reversibility in the solid state.