Guanzhong goat is one of the major dairy goats in China and its milk is also a major milk supply for the Chinese dairy industry. Whey protein has a balanced nutritional value and certain biological functions. To explore the proteomics of Guanzhong goat whey, whey fraction was separated from goat mature milk, and analyzed using iTRAQ-coupled LC-MS/MS. A total of 368 whey proteins were identified and quantified in the serum fraction, of which only 7% belong to goat, whereas 57% pertain to sheep, and 36% are homologous to bovine. The identified proteins were categorized according to their biological processes, cellular components, and molecular function based on their gene ontology annotation. The main biological processes involved were response to regulation of biological functions, metabolic process, and response to stimulus. The most general cellular components was extracellular (37%), and the most common molecular functions was protein binding, representing 46%. The data could provide important information for understanding the composition and unique biological properties of goat milk.