Hospital-acquired infections (HAIs) pose a significant threat to patient safety and well-being, contributing to increased morbidity, mortality, and healthcare costs. Nurses, as frontline healthcare providers, play a crucial role in preventing and controlling HAIs. This review article aims to investigate the multifaceted role of nurses in the prevention of HAIs, focusing on their responsibilities, challenges, and the impact of their interventions. The review will encompass an analysis of current literature, guidelines, and best practices related to nursing strategies for HAI prevention. The review will begin by examining the epidemiology and burden of HAIs, emphasizing the need for effective prevention strategies. It will then delve into the specific responsibilities of nurses in HAI prevention, such as adherence to infection control protocols, surveillance, and patient education. Furthermore, the review will explore the challenges faced by nurses in implementing HAI prevention measures, including understaffing, resource limitations, and organizational barriers. A critical analysis of nursing interventions and best practices for HAI prevention will be conducted, encompassing the use of evidence-based practices, technological advancements, and interdisciplinary collaboration. The review will also highlight the impact of nurse-led initiatives on reducing the incidence of HAIs and improving patient outcomes. In addition, the review will address the importance of education and training for nurses in infection prevention and control, as well as the role of leadership and organizational support in fostering a culture of safety and accountability. Furthermore, the review will discuss the potential for future research and innovation in empowering nurses to further enhance their role in HAI prevention. Overall, this review aims to provide a comprehensive understanding of the pivotal role of nurses in preventing HAIs and to underscore the significance of supporting and empowering nursing professionals in this critical aspect of patient care.