Goat (Capra hircus) has always been a source of fibre for human use and holds an important place in international high-end textiles. Fibre diameter is the most concerned economic indicator for producers. Understanding the formation mechanism of fibre diameter and related key proteins can help optimize and control the production of cashmere. Although mass spectrometry (MS)-based workflows have made great progress in achieving near-genome-wide coverage, the equivalent complete map of cashmere proteome is still elusive. Here, we performed label-free liquid chromatography coupled with tandem MS to profile the cashmere proteome. Firstly, by measuring the fibre diameter, it was found that the average fibre diameter of Alxa cashmere was significantly smaller than that of Alpas. With the help of proteomics technology,170 proteins were detected with high confidence. A total of 68 differentially expressed proteins were identified in the two cashmere, 131 proteins were specifically expressed in Alpas, and 40 proteins were specifically expressed in Alxa. Through Gene Ontology enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes, Protein-Protein Interaction network construction, and the CytoHubba plugin of the Cytoscape software were used to interpret the proteomic data. Finally, KRT10, KRT14, KRT17, and KRT82 played a key role in leading to the difference in the diameter of the two fibres. Combined with bioinformatics, the structure and function of these proteins were further studied to provide a more com-prehensive perspective for understanding the regulation mechanism of cashmere diameter. At the same time, combined with the information on genetics and gene expression, the genetic factors and epigenetic regulation mechanisms affecting cashmere fibre diameter can be further studied.