BACKGROUND: Solid-state nanopores are more suitable than biological nanopores for applications requiring durability and operation across a wider range of external parameters. However, the current solid-state nanopores prepared by various methods have the problem of poor stability, which limits the reproducibility of solid-state nanopore experiments and further wide application in the field of biochemical detection. So far, the problem of poor stability of nanopores has not been effectively solved. Therefore, it is still an urgent problem to explore effective experimental protocols to obtain solid-state nanopores with high stability. RESULTS: In this study, we dynamically monitored the instability of solid-state nanopores by high-resolution transmission electron microscopy and examined the effect of instability on the open-pore conductance of solid-state nanopores. In order to obtain long-term stability of solid-state nanopores, we used a chemical modification protocol to cover the surface of the solid-state nanopores with a dense protective film and demonstrated the reproducibility of our protocol through TEM characterization and extensive data statistics. Finally, we used long-lived solid-state nanopores to dynamically monitor the process of DNA synthesis by polymerase for more than 10 h, and calculated that the synthesis rate of polymerase was about 1.33-1.78 kb/min. SIGNIFICANCE: Long-term stability of solid-state nanopores are essential for its future development. Our observation of the unstable behavior of solid-state nanopores and the exploration of solutions will promote the wider application of solid-state nanopores in biochemical detection and other fields.