Updated project metadata. In the present study, a quantitative proteomic approach was used to analyse and compare the proteome in horns from endangered species (rhinoceros, Saiga antelope, and Tibetan antelope) and common species (yak, water buffalo, and goat) based on the isobaric tag for relative and absolute quantification (iTRAQ) techniques. In total, 591 proteins were identified, and 321 were quantified and categorised based on molecular function, cellular component, and biological process. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) results based on differences in the amount of protein identified three major clusters, and proteins including transglutaminase, desmocollin, and elongation factors were selected as trait components from proteomic patterns of horn samples from different species. Quantitative proteomic analysis-based strategies can therefore provide further evidence for sustainable alternatives to replace animal horn from threatened species.