Developing customizable pH-responsiveness for supramolecular hydrogels is of great significance and has drawn tremendous attention. Through systematic simulation analysis, we formulated a simple supramolecular hydrogel (i.e., poly(AAm-co-NaSS)/BSA on the basis of electrostatic interaction between the sulfonate groups of poly(AAm-co-NaSS) and the protonated side groups of BSA, and proposed a novel pH-responsive mode for it: changing the internal electric charge composition of the hydrogel through pH-induced ionization/protonation transition of BSA, thereby regulating the structural stability/shrinkage/extension of the supramolecular network. On basis of this theory, the pH-responsiveness of the poly(AAm-co-NaSS)/BSA hydrogel, in principle, could be pre-designed by adjusting the initial BSA/NaSS ratio. In this regard, we fabricated a poly(AAm-co-NaSS)/BSA hydrogel prototype with a BSA/NaSS ratio of 1/57 and investigated its rheological/swelling/disassembling behavior under different pH conditions (1.7, 4.7, 7.7, 10.7, and 13.7). In addition, we also prepared two capecitabine-loaded poly(AAm-co-NaSS)/BSA hydrogel prototypes with BSA/NaSS ratios of 1/57 and 1/102 respectively at pH 4.0, and compared their drug release behavior in SGF and SIF. Finally, the experimental results fitted well with our theoretical expectations, which testified the rationality of our assumption. Thus, we believed that the poly(AAm-co-NaSS)/BSA supramolecular hydrogel could find diverse applications in the future.