It is important to study the bactericidal mechanism with nanostructures for the design and preparation of high-efficiency sterilization materials. In this paper, the interfacial energy gradient between cells and nanopillars is proposed to be the driving force to promote cells to migrate into nanostructures and get killed. The expressions of interfacial energy and its gradient were first established, then the deformation of cells pressured by nanostructures was calculated. The results show that the interfacial energy gradient or the pressure on cells is influenced by nanopillar parameters substantially. The smaller the nanopillar diameter and the larger the pitch, the greater the pressure on cells. Only high enough nanocolumns can ensure sufficient cell creep deformation and become punctured. Furthermore, a cell volume and its adhesion morphology also influence the interaction between cells and nanostructures. The smaller the cell volume, the greater the pressure on it. And the larger the contact angle of adhered cells, the greater the pressure on the cells by nanopillars. Besides, the wettability of substrate material also influences the interaction between cells and nanopillars. It can be concluded that the model is reasonable and reliable since its calculation results are in good accordance with the experimental measurements.