Objective To systematically summarize the best evidence for the prevention of peripherally inserted central venous catheter (PICC)-associated infection, and provide evidence-based basis for healthcare workers to formulate management strategies for the prevention of PICC-associated infection. Methods According to the "6S" model of the evidence pyramid, relevant literatures on the prevention of PICC-related infection were systematically retrieved from top to bottom from UpToDate, websites of World Health Organization, Centers for Disease Control and Prevention, Infusion Nurses Society, Registered Nurses’ Association of Ontario, New South Wales Agency for Clinical Innovation, National Health Commission of the People’ Republic of China, Medlive, PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and SinoMed Database. The types of included literatures were clinical decision-making, guidelines, consensus, evidence summaries, and systematic reviews. The retrieval search window was from the establishment of the database to August 2024. Two researchers independently evaluated the quality of literatures and extracted evidence. Results A total of 19 papers were included in the analysis, including 2 clinical decisions, 9 guidelines, 6 expert consensuses, 1 evidence summary, and 1 systematic review. Ultimately, 28 pieces of evidence covering 6 topics including management, tools, catheterization, maintenance, infusion, and removal were formed. Conclusion This study summarizes the best evidence for preventing PICC-related infection, and recommends that clinical healthcare workers apply relevant evidence rationally and prudently, so as to reduce the incidence of PICC-related infections.