Acid-stress chaperone HdeA and its substrate protein, can contribute to pathogenic-bacteria survival by mutual interactions, when bacteria exposed to extremely acidic conditions. To figure out this mechanisms, molecular docking and molecular dynamics simulation were performed in this paper to investigate the binding mode of SurA to HdeA. MM-PBSA method was used to calculate the binding free energy. The interaction mode, H-bond and energy decompositions of the HdeA-SurA complex were firstly analysed. Based on these analysis, the key amino acid residues which are essential for interactions were subsequently determined. Our results may provide a theoretical guidence for exploring binding mechanism between HdeA and substrate as well as a new strategy for the development of new HdeA inhibitors.