Liquid-liquid extraction is a complex process that occurs at the interface between the aqueous and organic phases. The central aspect of this process is the formation of metal-ligand complexes. The hardness of chemical species, as defined by the hard and soft acid and base (HSAB) theory, is often considered to be a key factor influencing the selectivity and efficiency of complexation. However, despite its significance, the quantitative relationship between hardness and selectivity has not been systematically analyzed. In this study, our objective was to investigate the correlation between selectivity and hardness, comparing it with other ligand parameters that influence the separation of lanthanides and actinides. Our results allowed us to state that the extractant design could not be reduced to the estimation of a single contribution of hardness or one of the other popular descriptors, but their combination may be used in predictive modeling.