Background: This research was conducted to evaluate the potential benefits of zinc sulphate in the prevention of radiation induced mucositis in patients who are being treated for head and neck cancers. Materials and Methods: Forty patients with proven cancers of head and neck were randomly divided into 2 equal groups that either received zinc sulphate or placebo (control group). Patients who received curative radiotherapy or chemoradiotherapy were instructed to take zinc sulphate capsules (30 mg) daily at 8 hours interval. They were to begin 10 days before the start of treatment and continued until 2 weeks after completing the schedule. Mucositis was evaluated weekly according to the Oral Mucositis Assessment Scale (OMAS). Results: In both groups (zinc and control) mucositis was evident during the first week but its prevalence was 40% and 70.5% in the zinc and placebo groups respectively at the end of this period. This difference was significant (p<0.0001). The mean severity of oropharyngeal mucositis increased after commencement of radiotherapy and reached to maximum intensity in the 4^th week. Control group showed higher severity (p<0.0001). In comparison with the placebo group, the mucositis score of OMAS in the zinc group was lower until at 2 weeks after end of the treatment (p=0.0001). Conclusion: The present study shows that Zinc sulfate is effective in reducing the severity of radiation induced oropharyngeal mucositis. In addition, it delays the development of mucositis and may be used at a lower dose (30 mg 3 times daily) with the same benefit but fewer side effects.