Dentine hypersensitivity is an annoying worldwide disease, yet its mechanism remains unclear. The long-used hydrodynamic theory, a stimuli-induced fluid-flow process, describes the pain processes. However, no experimental evidence supports the statements. Here, we demonstrate that stimuli-induced directional cation transport, rather than fluid-flow, through dentinal tubules actually leads to dentine hypersensitivity. The in vitro/in vivo electro-chemical and electro-neurophysiological approaches reveal the cation current through the nanoconfined negatively charged dentinal tubules coming from external stimuli (pressure, pH, and temperature) on dentin surface and further triggering the nerve impulses causing the dentine hypersensitivity. Furthermore, the cationic-hydrogels blocked dentinal tubules could significantly reduce the stimuli-triggered nerve action potentials and the anion-hydrogels counterpart enhances those, supporting the cation-flow transducing dentine hypersensitivity. Therefore, the inspired ion-blocking desensitizing therapies have achieved remarkable pain relief in clinical applications. The proposed mechanism would enrich the basic knowledge of dentistry and further foster breakthrough initiatives in hypersensitivity mitigation and cure.