The determination of permeability parameters is the basis of seepage analysis in hydraulic engineering, and the inversion of them is one of the effective means to obtain the material permeability coefficient of the project. In order to quantify the influence of permeability coefficient of the main zone of a ship lock on the seepage field of the hub, a three-dimensional seepage finite element analysis model of the large ship lock was established. The waterhead values of different measuring points were taken as indicators, and the three-level orthogonal tests with the permeability coefficient of the concrete lock body, bedrock, anti-seepage curtain and drainage hole as factors were designed to carry out the sensitivity analysis of permeability coefficient of each zone to the ship lock seepage field. Then, the material permeability coefficient of the main zone was inversely determined by variable tolerance method. The results show that the sensitivity of the permeability coefficient of each zone to the waterhead of the measuring points was curtain, bedrock, hole curtain and concrete from high to low, among which the influence of curtain, bedrock and hole curtain were more significant. So, the inversion should focus on the permeability coefficient of the zones of high influence such as the curtain and bedrock. The maximum error between the calculated and measured values of inversion was 2.37%, and the permeability coefficients of the curtain and bedrock were 3.04×10-6 and 5.51×10-6 cm/s, respectively. The inversion parameters can be used for the seepage stability analysis of the ship lock, and the research results can provide some reference for similar projects.