Objective <p>This pilot study aims to investigate the role of microRNAs (miRNAs) as early diagnostic biomarkers for asbestos-related respiratory diseases.</p> Methods <p>We conducted a pilot study to explore the plasma miRNA profile in 28 subjects, including 9 unexposed population controls, 9 ILD-free subjects formerly exposed to asbestos, and 10 cases of asbestos-related interstitial lung disease (ILD). Current smokers or subjects with other lung diseases were excluded. We used the receiver operator characteristic (ROC) area under the curve (AUC) to estimate the potential diagnostic accuracy of miRNAs. We also conducted a meta-analysis to estimate the pooled quantitative diagnostic accuracy of the differentially expressed miRNAs, based on their AUC and related 95% confidence intervals (CIs).</p> Results <p>In total, 346 miRNAs were detected in the plasma samples of all study subjects. Both, miR-3679-5p and miR-574-5p, showed a 89% diagnostic accuracy (95% CI 0.73–1.00) in discriminating ILD-free asbestos-exposed from unexposed subjects. miR-6516-5p, miR-942-5p, and let-7f-5p showed a 92% diagnostic accuracy (95% CI 0.76–1.00) in differentiating asbestos-related ILD cases from ILD-free subjects formerly exposed to asbestos. miR-4714-3p and miR-20a-5p showed a 91% diagnostic accuracy (95% CI 0.78–1.00) in discriminating asbestos-related ILD cases from unexposed subjects.</p> Conclusion <p>We successfully tested the effectiveness of our standard operating procedures in detecting differences in the plasma miRNA expression between subjects formerly exposed to asbestos, with and without interstitial lung disease and unexposed controls. Our results suggest that the plasma microRNA profile might be a potential biomarker of asbestos-related lung diseases.</p> Graphical abstract <p></p>