Among the numerous adsorption strategies for DNA adsorption into mesopores, the salt-solution-induced adsorption method has a great application potential in nucleic acids science; thus, it is important to understand the adsorption mechanism. This work demonstrates the mechanistic aspects underlying the adsorption behaviors of DNA with mesoporous silica nanoparticles (MSNs) in aqueous solution. The driving forces for the adsorption process can be categorized into three parts: the shielded electrostatic force, the dehydration effect, and the intermolecular hydrogen bonds. Compared to the adsorption behaviors of DNA with a solid silica nanosphere, we find some unique features for DNA adsorption into the mesopores, such as increasing the salt concentration or decreasing the pH value can promote DNA adsorption into the mesoporous silica. Further analysis indicates that the entrance of DNA into mesopores is probably controlled by the Debye length in solution and DNA can generate direct and indirect hydrogen bonds in the pores with different diameters. The following desorption study depicts that such types of hydrogen bonds result in different energy barriers for the desorption process. In summary, our study depicts the mechanism of DNA adsorption within mesopores in aqueous solution and sets the stage for formulating MSNs as carriers of nucleic acids.