Abstract: Driven by the requirements of in-situ analysis tasks in China’s “Lunar Exploration Phase 4”project, it is of great significance to study the performance of ceramic knife-edge seals under the interference of lunar dust. This article introduces various sealing structures at home and abroad and proposes a sealing method of ceramic knife-edge extruding polytetrafluoroethylene. Through theoretical analysis and ANSYS simulation, it is determined that the sealing effect is optimal when the tip radius of the knife-edge is R0.5mm. A lunar dust contamination experimental platform is built for tests. The results show that an increase in the amount of lunar dust contamination significantly increases the leakage rate, and increasing the sealing force can compensate for the negative impact of lunar dust to a certain extent, providing a reference for the sealing technology of lunar in-situ sampling and detection.