In this study, we compared the effects of gamma and high-energy proton radiation (1000 MeV) on DNA in aqueous saline solutions (5 and 150 mM NaCl) at doses of 30 and 50 Gy. We used spectral methods (the ultraviolet absorption method, spectrophotometric methods for nucleic acid quantification, spectrophotometric DNA melting, and circular dichroism) for the estimation of the number of damaged nitrogenous bases and damage of the secondary DNA structure. It was found that under these conditions, proton radiation causes more severe destruction of nitrogenous bases and the secondary DNA structure than exposure to gamma rays at the same dose. In DNA irradiated with protons, the formation of crosslinks is possible and the probability for crosslinking increases with the increase of the ionic strength of the irradiated solution.