Objectivesto compare saliva proteome of patients before treatment of head and neck cancer and six months post-treatment with controls. DesignFive dentate patients and five age and gender-matched controls were included. The stimulated salivary secretion rate was determined, and saliva was stored at −80 °C. After thawing, 30 mg of each sample and a reference (aliqouts of all samples) 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. Data are available via ProteomeXchange with identifier PXD047500. Results966 proteins with ≥2 unique peptides were found. Compared with controls, 30 proteins were found in significantly lower relative abundances and 65 in higher at pre-treatment and 38 proteins in significantly lower relative abundances and 34 proteins in higher post-treatment. Regarding proteins from the salivary glands, a significantly lower relative abundance of Cystatins was detected pre-treatment and significantly 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 relative abundance of mucins and dry mouth, sticky saliva and problems with swallowing was detected. ConclusionDecreases in several salivary gland 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.