Background: Immunonutritioncontrols the response of the body to disease and damage. Glutamine acts to maintain the intestinal tract, immune cells and muscle, thus it is important to attack against infections and mucositis, also modifies the inflammatory response. Arginine plays a significant role in cell proliferation, synthesis of protein, endocrine, and immune control. So they help to reduce the degree of toxicities induced by treatment. Objective: This study aimed to evaluate the effects of immunonutrition formula administration on the incidence of acute radiotherapy (RT) related toxicities, treatment interruption, overall treatment time and response to treatment. Patients and methods: This prospective study included 120 patients who met the inclusion criteria (adults > 18 years old, pelvic malignancy; bladder, prostate, cervix, uterus and rectum who received radical dose radiotherapy; adjuvant, neoadjuvant, or definitive, either alone or with chemotherapy or hormonal treatment, and PS 0-2). Patients were randomized into 2 groups: Group 1 received immunonutrition with planned calculated diet and standard treatment, and group 2 that received standard treatment only with standard nutrition. difference regarding percentage of body weight loss, development of toxicity, time to recovery from toxicity, incidence of hospital admission, and treatment interruption, which were lower in group 1 (P value < 0.0001, 0.022, 0.001, 0.021, and 0.022 respectively). By multivariate logistic regression, group 1, diagnosis of bladder and rectal cancer were independent predictors of toxicity (P value 0.045, 0.026, and 0.001 respectively). Conclusion: Arginine, glutamine, fish oil immunonutrition formula administration could reduce the incidence of radiotherapy-related toxicities, hospital admission, treatment gap and prevent weight loss.