By using correlation coefficient analysis, linkage disequilibrium, and haplotype network construction, we found three non-synonymous SNPs (R597E, T595I, and G572S) in exon 5 and two synonymous SNPs in exons 8 and 16 in <i>DSG3.</i> These mutations significantly segregated high- and low-altitude goats in two clusters, indicating the contribution of <i>DSG3</i> to the high-altitude hypoxia adaptation in the Tibetan goat.