Salt lakes on the Tibetan Plateau (TP) are rich in lithium (Li), boron (B) and other mineral resources, and accurate assessment of the mineral content and spatial distribution of the brine in those salt lakes is important to guide the development and utilization of their mineral resources. There are few studies estimating the mineral content of salt lakes on the TP due to the lack of in situ investigation data. This study introduced an intelligent prediction model combining a feature selection algorithm with a machine learning algorithm using Sentinel-2 satellite data to estimate the Li, B, and TDS contents of Bieruoze Co and Guopu Co lakes on the TP. First, to enrich the spectral information, four mathematical transformations (reciprocal, logarithmic, reciprocal of logarithm, and first-order derivative) were applied to the original bands. Then, feature selection was performed using the genetic algorithm (GA) to select the optimal input variables for the model. Finally, prediction models were constructed by partial least squares regression (PLSR), multiple linear regression (MLR), and random forest (RF). The results showed that: 1) The spectral mathematical transformation provided rich spectral information for the mineral content estimation. 2) The performance of the estimation model constructed by the feature optimization method using GA was better than that of the estimation model constructed based on all spectral bands. Based on GA for feature optimization, the MAPE of GA-RF for estimating Li, B and TDS contents on the testing set was reduced by 77.52%, 28.54% and 36.79%, respectively. 3) Compared with the GA-MLR and GA-PLSR models, GA-RF estimated Li (R2=0.99, RMSE=1.15 mg L-1, MAPE=3.00%), B (R2=0.97, RMSE=10.65 mg L-1, MAPE=2.73%), and TDS (R2=0.93, RMSE=0.60 g L-1, MAPE=1.82%) all obtained the optimal performance. This study showed that the combination of the GA-based feature selection method and the RF model has excellent performance and applicability for monitoring the content of multiple minerals using Sentinel-2 imagery in salt lakes on the TP.