The folding and unfolding of nucleic acids (DNA and RNA) are essential for these functions in cells. These behaviours are also widely used for various technical applications using nucleic acids. To understand the biological mechanism of nucleic acids function and design materials of nucleic acids, the biophysical approach using thermodynamics is highly useful and important. The stability prediction of duplexes of nucleic acids have been developed and widely used. However, it has been also noted that such predictions cannot be always adopted to prediction in various solution conditions, especially the cellular conditions, because the concentrations of cations and cosolutes in the intracellular condition termed molecular crowding are different from those in the standard experimental condition. Moreover, the crowding condition in cells is spatiotemporally variable. Therefore, it is highly demanded to establish the prediction method available in cellular conditions for the stability of various structures of nuclei acids. This article reviews the biophysicochemical background predicting nucleic acids stability and our recent studies for the prediction of these stability in the cellular conditions