Abstract Objectives: to compare saliva proteome of head and neck cancer patients prior to treatment and six months post-treatment with that of controls and relate the level of mucins with patient’s problems with dry mouth, sticky saliva and swallowing. Design: Five dentate patients and five age and gender matched controls were included. The stimulated salivary secretion rate was determined and saliva stored at -80°C. After thawing, 30 mg of each sample and a reference was trypsin digested. The digested peptides were analyzed by mass spectrometry. The relative abundances were transformed to log2 and significant differences determined. Relative abundances of mucins were compared with patient’s problems with dry mouth, sticky saliva and swallowing. Results: 966 proteins with ≥ 2 unique peptides were found. Compared with controls, 21 proteins were found in lower relative abundances and 30 in higher at pre-treatment and 28 proteins in lower relative abundances and 24 proteins in higher post-treatment. Regarding saliva proteins, a lower relative abundance of Cystatins was detected pre-treatment and lower relative abundances of Cystatin, Cysteine-rich secretory protein 3, Lactoperoxidase, Prolactin-inducible protein and Proline-rich protein 4 post-treatment. No clear relation between mucins and dry mouth, sticky saliva and problems with swallowing was detected. Conclusion: Decreases in several saliva proteins post cancer treatment might lead to a reduced defense against oral disorders. Knowledge about changes in saliva proteins in connection with oral cancer treatment is important for planning dental care for these patients.