Protection and deprotection of the 2'-hydroxyl group of RNAs are critical for RNA-based drug discovery. This paper reports development of a bioreduction labile protecting group of the 2'-hydroxyl group in RNA. After the reduction of the nitro group in a chemical or enzymatic manner, the protecting groups were removed spontaneously. The attachment of electron-donating groups to the benzene ring or benzylic carbon enabled fast and controllable deprotection of the 2'-hydroxyl protecting group under physiological conditions.