Lithium (Li) isotopes are a promising proxy for silicate weathering in rivers. Cation exchange is a key mechanism for regulating river water chemistry, especially in high-erosion sedimentary basins. However, the influence of cation exchange on the sensitivity of this proxy remains unclear. Using spatially distributed samples from the Huanghe River, characterized by high erosion and sediment loads, we investigated the effect of cation exchange on dissolved Li isotopic composition (S7Lidiss) and evaluated other factors, such as lithology, climate, and topography. Despite broad climatic and topographic gradients and variable weathering intensities, mainstream S7Lidiss values show only a slight downstream increase (average + 18.3 +/- 1.2 parts per thousand, 1SD). This relative stability contrasts sharply with that of other large rivers. Our results suggest that these S7Lidiss variations are regulated primarily by an interplay between secondary mineral formation and cation exchange. Specifically, secondary mineral formation during silicate weathering increases S7Lidiss by preferentially incorporating 6Li into clays. This process is mainly driven by topography through its influence on water residence time. Subsequently, cation exchange with Ca and Mg releases previously adsorbed Li (low S7Li) from clays back into the river water, thereby decreasing S7Lidiss and buffering the expected increase in S7Lidiss by chemical weathering. Moreover, other potential factors, including source mixing (e.g., evaporite, salt-lake, tributary, and groundwater), climate, and carbonate precipitation, have minor or indirect influences on S7Lidiss. Our findings highlight that cation exchange can reduce the sensitivity of S7Lidiss to weathering intensity, potentially obscuring the silicate weathering signal in high-erosion sedimentary basins. Given the widespread presence of such basins, this buffering effect may be more significant than previously recognized. Thus, the sensitivity of Li isotopes as a silicate-weathering proxy and their impact on the marine record should be reassessed, particularly during periods of high erosion.