Mesoscopic coarse-grained simulations are adopted to investigate interfacial mechanisms of hydrophobic charged induction chromatography for protein purification by regulating pH. Simulations results indicate that: (i) lysozyme can be adsorbed mainly with top end-on and bottom end-on orientation on hydrophobic surfaces, dominated by the two hydrophobic regions located at both ends of lysozyme's long axis. Elution from the top end-on orientation is more difficult than that from the bottom end-on orientation; (ii) a higher ligand density can get a faster adsorption rate and stronger adsorption. Interestingly, the effect of ligand density on the desorption is mainly determined by the distribution probability of the positively charged groups of ligands; (iii) a higher ionic strength can lead to a wider orientation distribution, a stronger adsorption and a lower elution rate. This work might provide an efficient way to optimize the operating conditions and designing novel ligands. (c) 2015 American Institute of Chemical Engineers AIChE J, 61: 2035-2047, 2015