Background: Tumor Lysis Syndrome (TLS) is a serious oncology emergency that happens following cancer treatment. The oncology nurses have an important role in the prevention of TLS. Insufficient nurses’ knowledge and practice about preventive measures regarding TLS lead to life-threatening situations for patients. Without preventive measures, this condition will occur as a complication. So, prevention is better than treatment. Study aim: Evaluate the effect of preventive measures on oncology nurses’ performance regarding tumor lysis syndrome. Design: A quasi-experimental design. Setting: Oncology department at Zagazig University Hospitals in the Al Sharkia governorate of Egypt. Subject: A convenience sample of available nurses (40), who work in the previously mentioned setting. Tools: A self-administered questionnaire to assess demographic characteristics of nurses and their knowledge about TLS and its preventive measures; observational checklists to assess nurses' practice of TLS preventive measures. Results: All nurses' knowledge and practice dimensions were improved post implementing the preventive measures program in addition to the presence of a statistically significant difference and improvement in total nurses' knowledge and practices, with the percent of improvement equal to 81.8% and 42%, respectively. Conclusion: The intervention of the preventive measures program of the nurses has a positive effect and effective role in improving their performance (knowledge and practice) regarding TLS. Recommendations: More research should be conducted with a large sample size and in different contexts to assess the impact of the program on nurses' performance and make generalizations. Key Words: Preventive measures, Nurses’ performance, Tumor Lysis Syndrome