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The aim of this study was to explore the potential role of extracellular matrix (ECM) regulated by miRNAs in lung function decline.We convened 270 silica dust exposed subjects and divided them into three groups according to lung function data. MiRNAs were measured by real-time quantitative polymerase chain reaction detecting system and ECM-related proteins were detected by enzyme linked immunosorbent assay. Data were analyzed by t test, Chi-squared tests, nonparametric Mann–Whitney U test, and Spearman rank correlation coefficient.Lower miR-200c and miR-29c were observed in subjects with severe lung function decline and higher ECM proteins were observed in subjects with mild or severe lung function decline. MiRNA and ECM were significantly correlated with FVC%, FEV1%, MMF%, and PEF% (r: 0.204 to 0.458, P < 0.01) and that miRNA were significantly correlated with ECM (r: 0.309 to 0.687, P < 0.01).The abnormal ECM regulated by miRNAs may play an important role in lung function decline associated with silica dust exposure.