The study was designed to evaluate the influence of hyperbaric oxygenation (HBO) therapy on salivary gland function and the growth of salivary Streptococcus mutans,Lactobacillus and Candida albicans in patients with head and neck tumours who had undergone radiation therapy. Sixteen patients were included, with radiation doses from 58 to 70 Gy. The first examination was performed at baseline before the first HBO therapy (33.7 ± 9 months after radiation therapy), and the second after 20 daily HBO therapies in a hyperbaric chamber at 2.5 ATA (absolute atmospheres), where patients breathed 100% oxygen for 90 min each day. Measurements of salivary flow, buffer capacity, saliva pH and colony density of S. mutans,Lactobacillus and C. albicans in stimulated saliva were conducted, and xerostomia grade was assessed. Salivary flow increased from 0.20 ± 0.1 to 0.39 ± 0.2 ml/min at the end of HBO therapy (p < 0.001). Salivary pH also increased from 6.0 ± 0.2 to 6.5 ± 0.1 (p < 0.05). The colony density decreased from the time at baseline to the end of HBO therapy for S. mutans (p < 0.001), Lactobacillus (p < 0.05) and the fungus C. albicans (p < 0.05). The xerostomia grade decreased from 2.63 ± 0.2 to 1.94 ± 0.2 after HBO (p < 0.001). There was no significant change in buffer capacity. The increased salivary secretion rate and salivary pH, and decreased S. mutans and Lactobacillus colony density that were observed after HBO therapy may reduce caries progression in those patients.