To uncover the adaptative mechanism of the alkaline Amur ide (Leuciscus waleckii) population in Lake Dali Nor, Inner Mongolia, China, five samples of two populations, including one alkali form from Lake Dali Nor (DL), and one freshwater form from the Songhua River (SH), Heilongjiang, China, i.e., its historical origin, were analyzed using whole-genome resequencing technology. A total of 983528 nonredundant short insertions and deletions (InDels, 1–29 base pairs) were obtained. Among them, 8176 InDels that were polymorphic between the DL and SH populations were identified. Then, using integrated analysis of the known strong positive selection signal regions between the DL and SH populations, we identified a total of 176 potential candidate genes potentially affecting alkali-saline adaptation. Enrichment analysis showed that the genes were enriched mainly in inflammatory immune responses, ion transport, and osmotic regulation. Furthermore, the candidate genes abcc1, atp2b1, slc4a4, slc7a2, and aqp4 for key regulatory processes of alkali-saline adaptation, such as osmotic regulation and acid-base balance, were identified via selective pressure analysis using EasyCodeML, MEME, and FEL. Analysis showed that purifying selection played a dominative role for all of these genes, but a few amino sites could be identified to be under positive selection in the selection model. Prediction of three-dimensional structure revealed that some sites of the two proteins SLC4A4 and SLC7A2 coincided or were very close to the ligand-binding sites, indicating that the positive selection pressure mediated by the alkali-saline stress may contribute to the development of rapidly adaptive evolution in Amur ide. Our findings provide a basis for further study and reveal key genes for alkali-saline adaptation in Amur ide.