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The Parker-Oldenburg method, as a classical frequency-domain algorithm, has been widely used in Moho topographic inversion. The method has two indispensable hyperparameters, which are the Moho density contrast and the average Moho depth. Accurate hyperparameters are important prerequisites for inversion of fine Moho topography. However, limited by the nonlinear terms, the hyperparameters estimated by previous methods have obvious deviations. For this reason, this paper proposes a new method to improve the existing Parker-Oldenburg method by taking advantage of the invasive weed optimization algorithm in estimating hyperparameters. The synthetic test results of the new method show that, compared with the trial and error method and the linear regression method, the new method estimates the hyperparameters more accurately, and the computational efficiency performs excellently, which lays the foundation for the inversion of more accurate Moho topography. In practice, the method is applied to the Moho topographic inversion in the South China Sea. With the constraints of available seismic data, the crust-mantle density contrast and the average Moho depth in the South China Sea are determined to be 0.535 g/cm3 and 21.63 km, respectively, and the Moho topography of the South China Sea is inverted based on this. The results of the Moho topography show that the Moho depth in the study area ranges from 5.7 km to 32.3 km, with more obvious undulations. Among them, the shallowest part of the Moho topography is mainly located in the southern part of the Southwestern sub-basin and the southern part of the Manila Trench, with a depth of about 6 km. Compared with the CRUST 1.0 model and the model calculated by the improved Bott’s method, the RMS between the Moho model and the seismic point difference in this paper is smaller, which proves that the method in this paper has some advantages in Moho topographic inversion.