Chromatography is pivotal in separation and analysis, necessitating continuous performance enhancements. Yet, conventional methods exhibit limitations. This study introduces a novel approach by incorporating a second ligand, pushing chromatographic performance boundaries. Notably, this method can integrate with most optimization techniques, fostering synergy. Hydrophobic charge-induction chromatography (HCIC) serves as the focal point. Initially, an optimal resin, influenced by ligand density, was targeted. Various densities of the second ligand were coupled, assessing performance enhancement. Characterization, including scanning electron microscopy and BET analysis, was conducted. Subsequently, optimization effects under different pH, salt, and flow rate conditions were systematically studied, involving both static and dynamic adsorption experiments. Emphasis was placed on comparing the performance effects of the second ligand. Results showcase significant chromatographic enhancement with the second ligand, synergizing with optimization strategies, achieving breakthrough performance. In the final phase, the resin proves effective in the separation and purification of hIgG from human serum, achieving 96.6% purity and 91.6% recovery compared to the control, with increments of 10.6% and 20.4%, respectively. Meanwhile，the resin with the second ligand, exhibits commendable repeatability and stability. In conclusion, this study underscores how the addition of a suitable second ligand can elevate chromatographic performance, offering a novel strategy to augment existing ligand libraries and enhance chromatographic capabilities.