Background: The aim of palliative care is to improve the quality of life among seriously ill and dying patients and their families. Nursing students report emotional distress and feelings of inadequacy to the complexity of palliative care. Simulation-based education serves as a link between classroom learning and clinical practice. This study aimed to determine the effect of simulation-based education on medical-surgical nursing students' knowledge and practices regarding palliative care for patients with cancer. Method: A quasi-experimental research design was used (pre- and post-test-one group) to achieve the aim of this study. Setting: The study was conducted in clinical medical-surgical laboratory skills, Faculty of Nursing affiliated to Sohag University. Subjects: The study was carried out on 700 nursing students first semester 1^st academic year as a convenient sample in 2024. Tools of data collection: Two tools utilized for data collection (1) Self-administered questionnaire including two parts, part one; to assess medical-surgical nursing student's personal data and part two; to assess medical-surgical nursing student's knowledge regarding palliative care for patients with cancer (2) An observational checklist to assess medical-surgical nursing student's practice during implementation of palliative care for patients with cancer. Results: There was a highly statistically significant difference between the studied medical-surgical nursing student's knowledge and practice. The vast majority of the studied medical-surgical nursing students had a satisfactory level of knowledge and most of them had adequate level of practice after implementing simulation-based education. There was a highly significant difference correlation between medical-surgical nursing student's knowledge and practice after simulation-based education than pre- education. Conclusion: The present study concluded that simulation-based education was a feasible strategy and had a positive effect on improving medical-surgical nursing student's knowledge and practices regarding palliative care for patients with cancer.  Recommendations: The study recommended that simulation-based education should be integrated as an effective method in medical-surgical nursing student's training regarding palliative care for patients with cancer. Replication of the study with a larger sample of students from different universities may have a more generalized effect.