In this paper, we use a molecular theory to study the anomalous switching of ssDNA monolayers. Here, both ssDNA–water and water–water hydrogen bonds and their explicit coupling to the ssDNA conformations are considered. We find that hydrogen bonding becomes a key element in inducing the anomalous switching of ssDNA monolayers. This finding accords well with the experimental observations. Based on our theoretical model, we predict that the anomalous switching induced by water vapor will be applicable to a wide range of hydrogen bonds polymers, and ssDNA–water hydrogen bonds and water–water hydrogen bonds hybridization will lead to the hydrogen-bond network formation of 3D ssDNA monolayers.