Using all‐atom molecular dynamics simulations with Joung–Cheatham ion parameters and the OPC water model, the osmotic pressure values of monovalent alkali metal chloride solutions (KCl and NaCl) were calculated and compared to experimental values. The simulated osmotic pressure data were overestimated at high concentrations. To close the gap between simulation and experiment, we attempted to modify the Lennard–Jones interaction parameters of the cation–water oxygen pairs explicitly using the unequal Lorentz–Berthelot combination rule, such that experimental osmotic pressure values for a range of concentrations were well reproduced. These novel ion parameters could be potentially beneficial to simulation studies of G‐quadruplex DNA molecules, where ions play a key role in their folding process.