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Circulating microRNAs (miRNAs) are key regulators of metabolic and inflammatory pathways involved in MASLD. However, their clinical utility as non-invasive biomarkers remain unclear. This review aims to clarify their diagnostic, prognostic, and therapeutic potential, addressing current gaps in the literature. Methods: Following PRISMA guidelines, we conducted a systematic review of 1149 studies from the PubMed and Scopus databases up to 2024, focused on circulating miRNAs in MASLD. Results: The most frequently studied miRNAs included miR-122 (35.56% of studies), miR-21 (18.89%), miR-34 (14.44%), and miR-192-5p (13.33%). Diagnostic accuracy varied among miRNAs, with miR-200 and miR-298 demonstrating AUROCs of 0.96 and 0.98, respectively, for MASLD detection. In MASH, miR-200, miR-298, and miR-342 exhibited near-perfect AUROCs of 0.99, while miR-122 showed values between 0.81 and 1.0. For HCC, miR-214 achieved an AUROC of 0.88, and miR-34a ranged from 0.73 to 0.76. Several miRNA panels demonstrated high diagnostic accuracy, with AUROCs up to 0.99, particularly in distinguishing HCC from other liver conditions. Prognostically, elevated miR-122 levels correlated with disease severity and fibrosis progression, while miR-21 and miR-223 were linked to obesity-associated MASH. Therapeutic interventions, including surgery, dietary modifications, and supplementation, were found to modulate miRNA profiles. Conclusions: MiRNAs exhibit strong potential as minimally invasive biomarkers for MASLD, contributing to improved diagnosis, prognosis, and therapeutic decision-making. Their stability and role in personalized medicine underscore their clinical relevance.<\/jats:p>","DOI":"10.1007\/s13105-025-01110-w","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T04:13:13Z","timestamp":1752639193000},"page":"589-609","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The use of circulating miRNAs for the diagnosis, prognosis, and personalized treatment of MASLD"],"prefix":"10.1007","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4484-8819","authenticated-orcid":false,"given":"Ana Luz","family":"Tobaruela-Resola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3228-9916","authenticated-orcid":false,"given":"Ferm\u00edn I.","family":"Milagro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-312X","authenticated-orcid":false,"given":"Paola","family":"Mogna-Pelaez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2018-6434","authenticated-orcid":false,"given":"Mar\u00eda Jes\u00fas","family":"Moreno-Aliaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6475-5387","authenticated-orcid":false,"given":"Itziar","family":"Abete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3926-0892","authenticated-orcid":false,"given":"Mar\u00eda \u00c1ngeles","family":"Zulet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"issue":"1","key":"1110_CR1","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/hep.29367","volume":"67","author":"N Chalasani","year":"2018","unstructured":"Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ (2018) The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American association for the study of liver diseases. 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