This study compares the genetic diversity, population structure, and differentiation between the wild Brachymystax tsinlingensis population from Heihe in the Qinling Mountains and the domesticated second-generation population, using whole-genome resequencing(WGR) of 28 individuals (6 wild, 22 domesticated). After filtering, 1,784,221 high-quality SNPs were analyzed. Nucleotide diversity (Pi) was 0.000286 (wild) and 0.000235 (domesticated); expected heterozygosity (He) was 0.4716 and 0.5277; observed heterozygosity (Ho) was 0.5427 and 0.5751, respectively. Runs of homozygosity (ROH) and Genomic inbreeding coefficient based on Runs of Homozygosity (FROH) indicate that, compared to the wild population, the level of inbreeding in the domesticated population has increased. Phylogenetic, PCA and ADMIXTURE analyses revealed that the wild population exhibited a relatively homogeneous ancestral genetic component, whereas the domesticated population exhibited more admixture. Genetic differentiation (FST = 0.0495) was low between the two populations. This study identified a panel of seven SNP markers through SNP screening and machine learning approaches, which can effectively differentiate between wild and domesticated populations. Overall, the domesticated second-generation population of Brachymystax tsinlingensis retains genetic characteristics of the wild population to a certain extent, valuable for conservation and breeding.