The mechanism of the Hofmeister series is not entirely clear, but does not seem to result from changes in general water structure, instead more specific interactions between ions and proteins and ions and the water molecules directly contacting the proteins may be more important. Simulation studies have shown that the variation in solvation energy between the ions and the surrounding water molecules underlies the mechanism of the Hofmeister series. A quantum chemical investigation suggests an electrostatic origin to the Hofmeister series. This work provides site-centred radial charge densities of the ions' interacting atoms (to approximate the electrostatic potential energy of interaction), and these appear to quantitatively correlate with many reported Hofmeister series for electrolyte properties, reaction rates and macromolecular stability (such as polymer solubility, and virus and enzyme activities).
Early members of the series increase solvent surface tension and decrease the solubility of nonpolar molecules ("salting out"); in effect, they strengthen the hydrophobic interaction.  By contrast, later salts in the series increase the solubility of nonpolar molecules ("salting in") and decrease the order in water; in effect, they weaken the hydrophobic effect.
The "salting out" effect is commonly exploited in protein purification through the use of ammonium sulfate precipitation. However, these salts also interact directly with proteins (which are charged and have strong dipole moments) and may even bind specifically (e.g., phosphate and sulfate binding to ribonuclease A).
Ions that have a strong "salting in" effect such as I and SCN are strong denaturants, because they salt in the peptide group, and thus interact much more strongly with the unfolded form of a protein than with its native form.  Consequently, they shift the chemical equilibrium of the unfolding reaction towards unfolded protein.