AbstractGas-phase enzymatic catalysis has been long pursued but not yet utilized in industrial processes due to many limitations. Herein, we report a hydroxyl-rich graphene oxide (GO) aerogel that can preserve the enzymatic activity and stability in an anhydrous gas flow by providing a water-like microenvironment. Lipase immobilized in the GO aerogel exhibits a 5 to 10-fold increase in apparent activity than the lyophilized lipase powder in transesterification of geraniol and vinyl acetate in the gas phase and maintains the initial activity for more than 500 h. The solid-state circular dichroism measurement confirms that the lipase keeps its native conformation in the aerogel, and the thermogravimetric analysis shows that water molecules essential for the lipase activity can be replaced by the hydroxyl groups at the GO surface. The versatility of this method is demonstrated for two other lipases with different structures, promising unprecedented applications of enzyme-GO aerogels to gas-phase enzymatic catalysis.