Background: Rectal cancer is one of the most common forms of cancer and one of the top cancer killers. One of the modalities treatment is radiotherapy that causes fewer side effects as fatigue, skin reactions, gastrointestinal disturbance, rectal bleeding and bladder irritation. Nurses play important role in providing care for rectal cancer patients treated by radiotherapy (pre, during and post) exposure to radiation. Aim; This study aimed to develop nurses`performance guidelines for patient with rectal cancer undergoing radiotherapy. This aim was achieved through the following: Assessing knowledge and practices of nurses caring for patients with rectal cancer undergoing radiotherapy & developing nurses`performance guidelines for patients with rectal cancer undergoing radiotherapy. Design; A descriptive explorative design was utilized for conduction of this study. Setting; The study was conducted at the Radiotherapy Department and Outpatients' Clinics for oncology at Qena University Hospital. Study Subject; A convenient sample of all available nurses (N=30). Tools; I, self-administered questionnaire, II, an observational checklists Result; 63.33% of the studied nurses had satisfactory total knowledge regarding rectal cancer and 60% of them had unsatisfactory of total practices regarding care of patients with rectal cancer undergoing radiotherapy. Conclusion;Nearly more than half of the studied nurses had satisfactory total knowledge and also more than half of them had unsatisfactory total practices regarding rectal cancer. There was no a statistical significant correlation between studied nurses of total score of knowledge and total score of practices. Recommendations; on-going and regular in-service educational programs regarding evidence-based guidelines should include care of rectal cancer patients before, during and after radiotherapy.