Background: Cancer is the second leading cause of death so the need for palliative care has increased to enhance patient's quality of life and alleviate suffering. Nurses' level of competency in palliative care is an important factor affecting the quality of care applied to patients. Palliative care competency is centered on understanding palliative care, personal traits and capabilities, and essential abilities to carry out professional obligations through practice. The current study aims to evaluate the effect of instructional guidelines on nurses' competency regarding palliative care for patients during the end stage of cancer. Research design: This research was carried out using a quasi-experimental design. Subjects: A convenience sample of fifty nurses who work at the Oncology Institution at Sohag University Hospital was included in the current study. Tools: To collect data two Tools were used: Tool (I) Structured Interview Questionnaire which included two parts; (1) demographic characteristics and nurses' knowledge regarding cancer and palliative care and Tool (2) Palliative Care Competency checklist. Results: After a month of implementing instructional guidelines, the current study found that nurses' overall knowledge scores had improved. There were statistically significant variations in all competency domains before and after a month of implementing the instructional guidelines. Conclusion: Implementing instructional guidelines has a positive impact on nurses' knowledge and competency related to providing palliative care to patients in the end stages of cancer. Recommendations: implementing competency-based nursing interventions for cancer patients in their advanced stages. Periodically, a continuous in-service training program should be held to update nurses' knowledge and raise their competency levels in palliative care.