Abstract: Background: Hospital-acquired infections (HAIs) are a significant concern in healthcare settings, leading to prolonged hospital stays, increased costs, and potential mortality. Nurses play a pivotal role in preventing HAIs through their knowledge, attitudes, and practices. However, they encounter challenges such as workload, limited resources, inadequate training, antibiotic resistance, communication barriers, and environmental factors. Objective: This review aims to investigate nurses' knowledge and understanding of the causes and prevention strategies of HAIs, identify their role in preventing such infections, assess current practices and protocols, identify challenges faced, and explore the impact of nurse-led interventions on reducing the incidence of HAIs. Conclusion: Nurses are essential in preventing HAIs by implementing infection control measures, educating patients, collaborating with multidisciplinary teams, and monitoring for potential outbreaks. Nurse-led interventions, including antimicrobial stewardship programs, are crucial in reducing the incidence of HAIs and combating antibiotic resistance. By addressing challenges and implementing effective strategies, nurses can enhance patient safety, improve healthcare outcomes, and create a safer environment in healthcare facilities.