Electroporation shows great potential in biology and biomedical applications. However, there is still a lack of reliable protocol for cell electroporation to achieve a high perforation efficiency due to the unclear influence mechanism of various factors, especially the salt ions in buffer solution. The tiny membrane structure of a cell and the electroporation scale make it difficult to monitor the electroporation process. In this study, we used both molecular dynamics (MD) simulation and experimental methods to explore the influence of salt ions on the electroporation process. Giant unilamellar vesicles (GUVs) were constructed as the model, and sodium chloride (NaCl) was selected as the representative salt ion in this study. The results show that the electroporation process follows lag-burst kinetics, where the lag period first appears after applying the electric field, followed by a rapid pore expansion. For the first time, we find that the salt ion plays opposite roles in different stages of the electroporation process. The accumulation of salt ions near the membrane surface provides an extra potential to promote the pore initiation, while the charge screening effect of the ions within the pore increases the line tension of the pore to induce the instability of the pore and lead to the closure. The GUV electroporation experiments obtain qualitatively consistent results with MD simulations. This work can provide guidance for the selection of parameters for cell electroporation process.