Silicon and lithium isotopes are increasingly used to trace current and past weathering processes. Herein, four soil profiles (SL1, SL2, XNC, and DP) in the karst critical zone in southwest China were studied. The bedrock of the SL1, SL2, and XNC profiles are limestone, while the bedrock of the DP profile is shale. By analyzing their major elements, trace elements, and mineral compositions as well as using Si and Li isotope methods, we were able to identify the material source of the laterite in southwest China and study its element behavior and isotope fractionation characteristics during the weathering process. The results show that the δ³⁰Si of the profiles overlying limestone (SL1, SL2, and XNC) range from −0.5‰ to 0.7‰, and those of the δ⁷Li range from 0.28‰ to 3.54‰, while the profile overlying shale (DP) has a large range of δ³⁰Si variation (from −1.2‰ to 1.1‰). The results reveal a clear inheritance from the underlying bedrock, indicating that the profiles reflect in-situ weathering. Although no obvious relationship exists among the chemical index of alteration (CIA), the δ³⁰Si, and the δ⁷Li, a significant correlation between δ³⁰Si and δ⁷Li indicates that the isotope fractionation of the studied profiles is mainly affected by the dissolution and formation of minerals during the weathering process, and the biological effect is relatively small. Further, a diagram of Li/Al versus δ⁷Li shows a decrease in both Li/Al and δ⁷Li during weathering.