The chemical etching liquid in landfills is very harmful to surface water and groundwater. At the same time, the chemical erosion effect will affect the stability of landfills. Thus, the liner structure design and realistic research of the anti-seepage system are the key. Aimed at the stability of the anti-seepage system, this paper analyzes the mechanical stability of the chemical anti-seepage material used in the anti-seepage layer of the landfill slope based on the limit equilibrium method, obtaining accurate safety coefficient of the liner damage of the landfill slope. On this basis, the anti-seepage chemical materials conforming to the safety coefficient standard are selected; in the design of the landfill anti-seepage system considering chemical erosion, there are holes or joint defects in the single-layer geomembrane liner, so the chemical etching liquid is likely to flow from the geomembrane hole. This paper proposes the practical anti-seepage scheme of HDPE geomembrane combined polymer chemical material GCL and compacted clay. At the same time, a three-dimensional composite geotechnical drainage net is added as a protective layer on the geomembrane, which can play an anti-seepage effect and guiding role for the landfill anti-seepage system under chemical erosion. The anti-seepage design proposed in this paper is of certain reference and guiding significance for the design of the landfill anti-seepage system considering chemical erosion.