Hydrogen sulfide (H2S) is the third endogenous gaseous signal molecule in organisms that can directly increase the salt tolerance of plants by closing the K+ channel. Inspired by the important role of H2S in nature, we have designed a H2S-responsive artificial nanochannel biosensor based on an azide reduction reaction strategy. This biomimetic device demonstrates an excellent H2S selective response owing to specific azide reduction by H2S inducing BSA aggregation on the channel with a high ion gating ratio. Furthermore, this H2S-responsive biosensor shows excellent reversibility and stability and a fast response rate, which will help us better understand the synergistic effect of H2S messengers in the ion channels of living organisms.