A facile approach for synthesizing superhydrophobic hollow silica micelles (SHSMs) with hydrophilic cores and amphiprotic (superhydrophobic/hydrophilic) shell structures that act as all-in-one smart nanomaterials is presented. The particles possess hydrophilic cores consisting of silica and a polyelectrolyte (PE) network and an amphiprotic shell consisting of superhydrophobic long-chained hydrocarbons and hydrophilic PEs. Due to the unique hydrophilic cores and amphiprotic shells, the particles exhibit extraordinary performance in terms of amphiprotic catalytic reactions in organic and aqueous solutions, oil/water separation and pollutant purification, and an ultrahigh loading capacity of enzymes with significant stability and efficient recyclability. The amphiprotic functionalities of the SHSMs have the potential to allow for a rich range of applications to be explored.