Linear adsorption isotherms were registered by a frontal analysis method for four substituted benzophenones (BPs) using a liquid chromatography Luna C18(2) column as adsorbent. The isotherm data points were measured at different mobile-phase compositions of methanol-water, varying the methanol volume fraction from 0.4 to 0.6 with a step of 0.05 and keeping the temperature at 30 degrees C. Henry's constants were obtained from the analysis of experimental data for each mobile-phase composition. The substituent effect on Henry's constant was evaluated, and it was found that the hydrogen-bond acceptor ability of the p-substituent, the interactions of the carbonyl group with the polar mobile phase molecules, and the molecular volume are key aspects governing the adsorption process of the studied BPs. In addition, the effect of the mobile-phase composition was analyzed by applying two different models to predict the Henry's constants and compare them to the experimental values. It was found that the Snyder model is the most suitable to describe the variation of the mentioned constant with the volume fraction of methanol in the mobile phase.