Electroporation refers to a biophysical process wherein cell permeability is altered by inducing pores of the cell membrane through application of an electric field. It has found extensive applications in cancer therapy and gene delivery. The alteration of electrical impedance during electroporation was investigated by synergistically employing a self-powered triboelectric nanogenerator (TENG) and electrical impedance spectroscopy (EIS), thus serving as a theoretical foundation for real-time efficacy assessment of electroporation in clinical settings. A self-powered electroporation experimental system was established, and the findings demonstrated that upon reaching the threshold level of cell transmembrane potential, the application time of electric field led to electroporation of the cells, resulting in a decline in the impedance value of the blood. As the electric field persists, the impedance value gradually diminishes; when the blood impedance value changes insignificantly, the degree of cell electroporation is saturated. During the process of tumor cell electroporation, the relationships between HeLa cell impedance Z* and time T and cell concentration C is Z* = 7×10−11T5- 4×10−8T4+9×10−6T3-8×10−4T2+0.0117T-9.3587 C+124.2. Simultaneously, the occurrence and reversibility of electroporation were verified through Propidium Iodide (PI) fluorescence staining. The numerical calculations presented in this paper are based on the extended HANAI theory. Furthermore, the simulations were conducted through finite element analysis and perform equivalent circuit fitting on the experimental data. The numerical and simulation results are consistent with the experimental findings, validating the study's establishment of a quantifiable relationship between electroporation degree and cell parameter Z*、Rc、Xc and RRBC. As evidenced, the alteration in electrical impedance spectra can effectively indicate the extent of electroporation. Therefore, it is expected that employing the EIS approach will become an effective means to measure the therapeutic efficacy of electroporation in future clinical applications.