Herein we report the 2-nitrobenzenesulfonamide group as a new chemical linker that responds to the difference in redox potential across the cellular membrane, toward the construction of siRNA-polymer conjugates. PEG-conjugated to siRNA via the 2-nitrobenzenesulfonamide group (PEG-sul-siRNA) exhibited highly selective siRNA release under intracellular conditions due to the exclusive presence of the GSH/GST combination in the cell. In addition, siRNA release from PEG-sul-siRNA under extracellular reductive conditions was dramatically suppressed relative to PEG-siRNA conjugates containing a conventional redox-sensitive disulfide linkage (PEG-disulfide-siRNA), indicating the enhanced extracellular stability of the 2-nitrobenzenesulfonamide group. The enhanced gene-silencing effect of PEG-sul-siRNA for cultured cells relative to PEG-siRNA, containing a non-cleavable carboxylic amide linkage (PEG-car-siRNA), confirmed the intracellular release of siRNA via the PEG-sul-siRNA system. These results suggest that the 2-nitrobenzenesulfonamide group could be a suitable chemical linker alternative to the conventional disulfide group.