In typical alteration extraction methods, e.g., band math and principal component analysis (PCA), the bands or band combinations unitized to extract altered minerals are usually selected based on empirical models or previous rules. This results in significant differences in the alteration of mineral mapping even in the same area, thus greatly increasing the uncertainty of mineral resource prediction. In this paper, an intelligent alteration extraction approach was proposed in which an optimization algorithm, i.e., a genetic algorithm (GA), was introduced into the PCA; this approach is termed GA-PCA and is used for selecting the optimized band combinations of mineralized alterations. The proposed GA-PCA was employed to map iron oxides and hydroxyl minerals using the most commonly adopted multispectral data, i.e., Landsat-8 OLI data, at the Lalingzaohuo polymetallic deposits, China. The results showed that the spectral characteristics of GA-PCA-selected OLI band combinations in the research area were beneficial for enhancing alteration information and were more capable of suppressing the interference of vegetation information. The mapping alteration zones using the GA-PCA approach had a higher agreement with known ore spots, i.e., 25% and 33.3% in ferrous-bearing and hydroxyl-bearing deposits, compared to the classical PCA. Furthermore, two predicted targets (not shown in the classical PCA results) were precisely obtained via analyzing the GA-PCA alteration maps combined with the ore-forming geological conditions of the mine and its tectonic characteristics. This indicated that the intelligent selection of mineral alteration band combinations increased the reliability of remote sensing-based mineral exploration.