Objective: To screen out the differentially expressed proteins in saliva from breast cancer patients with white tongue coating and yellow tongue coating and subjects from healthy control group in order to find a biomarker for the early diagnosis of breast cancer and explore the mechanism and principle behind the formation of the tongue coating in traditional Chinese medicine (TCM). Methods: Breast cancer patients with thick white tongue coating and thick yellow tongue coating were enrolled, 10 patients for each group, and 10 normal individuals with thin white tongue coating were also enrolled. Proteins were extracted from the serum of the subjects, underwent denaturation, reduction and enzymolysis, labeled by isobaric tags for relative and absolute quantitation (iTRAQ) and identified by ESI-QTOF-Q II mass spectrometer. Peak spectrum were obtained, and analyzed by Data Analysis, MASCOTT 2.2 Searching and Scaffold. Then the results of differential expression were obtained. Results: There were 464 proteins identified, and 125 proteins met the strict quantitative criteria. Compared with heath control, 11 differentially expressed proteins were selected for breast cancer patients, with white tongue coating and yellow coating, while 26 differentially expressed proteins were selected between breast cancer with white tongue coating and yellow tongue coating. Conclusions: iTRAQ combined with liquid chromatography linked to tandem mass spectrometry (LC-MS/MS) analysis could swiftly and effectively perform proteomics study on differentially expressed proteins in saliva. And certain proteins closely connected with the occurrence of breast cancer and mechanism behind formation of tongue coating of TCM were also discovered.