Abstract Background Variability and inaccuracies in the diagnosis of prostate cancer, and the risk of complications from invasive tests, have been extensively reported in the research literature. To address this, the use of artificial intelligence (AI) has been attracting increased interest in recent years to improve the diagnostic accuracy and objectivity. Although AI literature has reported promising results, further research is needed on the identification of evidence gaps that limit the potential adoption in prostate cancer screening practice. Methods A systematic electronic search strategy will be used to identify peer-reviewed articles published from inception to the date of searches and indexed in CINAHL, IEEE Xplore, MEDLINE, Scopus, and Web of Science Core Collection databases. Registries including Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP) will be searched for unpublished studies, and experts were invited to provide suitable references. The research and reporting will be based on Cochrane recommendations and PRISMA guidelines, respectively. The screening and quality assessment of the articles will be conducted by two of the authors independently, and conflicts will be resolved by a third author. Discussion This systematic review will summarise the use of AI techniques to predict the need for prostate biopsy based on clinical and demographic indicators, including its diagnostic accuracy and readiness for adoption in clinical practice. Systematic review registration PROSPERO CRD42022336540
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