Abstract: Historically, the Red River served as the outlet to the sea for major rivers in the eastern edge of the Tibetan Plateau and is currently one of the main sources of sediment to the northern South China Sea. It is an ideal region for studying the source-sink processes and tectonic-climate-weathering relationships in the South China Sea since the uplift of the Tibetan Plateau. To understand the main controlling factors of silicate weathering in the catchment, we compared the major element characteristics and CIA (chemical index of alteration) of sediments with different grain sizes in the Red River and its tributaries, and analyzed the correlation between CIA and environmental parameters regarding climate, topography, and lithology. Results indicate that coarse-grained sediments are a mixture of quartz and feldspar, and their major element content is significantly influenced by grain size effects and quartz dilution effects, showing no correlation with any environmental parameters. Hence, their CIA may not accurately reflect chemical weathering. In contrast, fine-grained sediments can represent the average composition of the upstream catchment, and their CIA primarily reflects the degree of chemical weathering in the catchment. Through the correlation analysis between the CIA of fine-grained sediments and environmental parameters, we found that rainfall and slope are the main controlling factors on weathering in the Red River catchment.