Abstract: Labyrinth seal is one of the most common sealing types in turbomachinery. Structural optimization of labyrinth seals can reduce fluid leakage rate and improve operational efficiency. In this paper, a novel flexible self-adaptive labyrinth seal is proposed. By incorporating flexible tooth structure in the end-stage sealing tooth, the deformation degree of the flexible tooth can be adaptively adjusted using the natural pressure difference formed in the flow field, thereby adjusting the sealing clearance. Fluid-structure interaction (FSI) analysis of flexible self-adaptive labyrinth seal based on computational fluid dynamics (CFD) and finite element method (FEM) is conducted. Deformation and flow characteristics of the seal under different operating conditions and various flexible tooth geometries are calculated to obtain the leakage characteristics, and then compared with the traditional labyrinth seal. The results demonstrate that the flexible self-adaptive labyrinth seal maintains low leakage level during changing operating conditions, reducing leakage rate by approximately 26% under high pressure ratios. Especially by increasing the length of flexible tooth and reducing its thickness, the flow contraction effect can be enhanced to improve the leakage control effect of the novel seal.