Abstract Using pyren-1-carboxyaldehyde as a fluorescent probe, alcohol and salt–DNA interactions have been studied and quantified in terms of free energies of binding. This quantification implies the determination of the “ true” free energy of binding of the probe, after correction through solubility measurements of the equilibrium binding constant of the probe to DNA. According to results, the interaction of alcohols is indirect and is based on the changes that they cause in the structure of water, changes which in turn alter the degree of hydration of DNA. On the other hand, salts interact with DNA through coulombic forces. A linear correlation between the free energy of binding for the different salts and the valency of the cations has been found.