Background: Oral mucositis is a major problem affecting all head and neck cancer (HNC) patients received radiotherapy. Till now, available treatment is just symptomatic with limited effects. Preventive strategies may be better to avoid this complication. Animal models studies have illustrated that anti-cancer treatment toxicity display prominent daily variations; therefore, undesirable side effects could be significantly reduced by administration of radiotherapy at specific times when they are better tolerated. Aim: To compare “soreness quality score” (SQS) between 2 groups of head and neck cancer patients received radiotherapy at different daily time. Methods: 2 groups of head neck cancer patients treated at Mansoura university hospital; each group included 80 cases. Group A received radiotherapy at early morning between 6 and 8 am, while Group B received radiotherapy in the afternoon between 1 and 3 pm. Oral mucositis survey was self-reported weekly during and at the end of treatment by using “soreness quality score” (SQS). Results: For group A, mild mucositis (score 1 and 2) was recorded in 53 cases (66%) and severe mucositis was recorded in 27 cases (34%). For group B, mild mucositis was recorded in 29 cases (36%) and severe mucositis was recorded in 51 cases (64%). There was statistically significant difference (0.003) between both groups as regards development of severe oral mucositis. Conclusion: Better toxicity profile as regards oral mucositis could be obtained by giving radiotherapy for (HNC) patients at early morning compared to late afternoon. Further studies are worthwhile to confirm our findings.