The present study seeks to evaluate the application of the 238U-234U-230Th radioactive disequilibrium methodology for the determination of the regolith production rates in thick weathering profiles marked by long histories, encountered under various climate regimes, but still very little studied by these techniques. For this purpose, 238U-234U-230Th disequilibria have been analyzed in the top 11 m of a lateritic profile developed on a granitic bedrock in south China (Longnan, Jiangxi Province) under a subtropical climate. The results demonstrate that in such a weathering profile the determination of weathering rates from the analysis of U-series nuclides in bulk rock samples cannot be recovered by applying in one step to the entire alteration profile the modeling approach classically used to interpret the U-series nuclides, i.e. the “gain and loss” model. The modeling has to be made on subsections of relatively small size (<1 or 2 m of thickness), so that the model assumptions can be met, especially the constancy of the mobility parameters along the weathering zone. The results also confirm that the upper part of the weathering profiles marked by the vegetation/biological influences and responding to the short-term climate variations is not well adapted for applying the U-series nuclides methodology for recovering regolith production rates. Based on the data, regolith production rates were estimated independently on four different deeper zones of the profile. Similar values of ~2 m/Ma have been obtained whatever the level, suggesting that such a profile of more than 5 million years would be formed at a relatively stable long-term production rate (averaged over several thousand years). This production rate is slow compared to the production rate deduced from previous in situ 10Be data, which can be explained by assuming non steady-state erosion of the upper part of the profile. Slow denudation rates similar to the U-series derived production rates of 2 m/Ma can thus be obtained with a minimum exposure time of 60 ky, and an inherited component of 20,000 atoms/g originating from the exhumed deeper part of the profile. Altogether the data demonstrate that the combined analysis of U-series and cosmogenic nuclides, which has the potential to become a relevant approach to constrain the dynamics of continental surfaces, requires (a) dense and deep sampling for both nuclides studies, and (b) also to consider more systematically the polyphased and variable history of erosion of the continental surface during the Quaternary.