This study examines the effect of different salt types on protein retention and selectivity in anion exchange systems. Particularly, linear retention data for various proteins were obtained on two structurally different anion exchange stationary-phase materials in the presence of three salts with different counterions. The data indicated that the effects are, for the most part, nonspecific, although various specific effects could also be observed. Quantitative structure retention relationship (QSRR) models based on support vector machine feature selection and regression models were developed using the experimental chromatographic data in conjunction with various molecular descriptors computed from protein crystal structure geometries. Star plots for each descriptor used in the final model were generated to aid in interpretation. The resulting QSRR models were predictive, with cross-validated r2 values of 0.9445, 0.9676, and 0.8897 for Source 15Q and 0.9561, 0.9876, and 0.9760 for Q Sepharose resins in the presence of three different salts. The predictive power of these models was validated using a set of test proteins that were not used in the generation of these models. Interpretation of the models revealed that particular trends for proteins and salts could be captured using QSRR techniques.