Aiming at the problem that the adaptability of the lip seal structure in the main drive sealing system of shield machine to the service condition is not clear, the finite element simulation models of the sealing structure under TBM and shield conditions are established respectively. In the orthogonal test, the waist thickness, lip front angle, axial compression, and radial compression of seal structure are selected as the research factors, and the unit radial force and contact width of the lip seal are taken as the response indices. The range and variance analysis are used to obtain the influence degree of each factor on the index under TBM and shield conditions. According to the the results of sensitivity analysis, the optimal structural parameters of lip seal under TBM and shield conditions are optimized respectively. The optimized sealing structure is verified by whether the ring with a wedge-shaped protrusion and under pressure. The results show that: （1）Under TBM condition, the pressure of 0 MPa with or without wedge-shaped protrusions, the optimal sealing structure has a certain decrease in the contact width and a significant increase in the unit radial force. (2)Under shield condition, with wedge-shaped protrusion and pressure bearing, the unit radial force and contact width of the optimal sealing structure are lower than those before optimization; and without wedge protrusion and pressure bearing, the unit radial force and contact width are basically the same as those before optimization.