Heatstroke (HS) is a life-threatening injury requiring neurocritical care which could lead to central nervous system dysfunction and severe multiple organ failure syndrome. The cell–cell adhesion and cell permeability are two key factors for characterizing HS. To investigate the process of HS, a biochip-based electrical model was proposed and applied to HS. During the process, the value of TEER is associated with cell permeability and CI which represents cell–cell adhesion decreases that are consistent with the reduction in cell–cell adhesion and cell permeability characterized by proteins (occludin, VE-Cadherin and ZO-1) and RNA level. The results imply that the model can be used to monitor the biological process and other biomedical applications.