Introduction: Extracellular matrix production by pleural mesothelial cell in response to M.tuberculosis contributes to tuberculous fibrosis. NOX4 is involved in the pathogenesis of tuberculous fibrosis. In this study, we evaluated whether the microRNAs targeting NOX4 genes showed protective effect in tuberculosis fibrosis. Methods: We selected probable candidate miRNAs that binds the 3’ UTR s of NOX4 gene by TargetScan prediction software. The role of miRNAs in tuberculous pleural fibrosis was studied using in vitro pleural mesothelial cell (PMC) experiments. Results: Heat-killed mycobacterium tuberculosis (HKMT) induces NOX4-ROS expression and downregulates the level of miRNA-148 in PMC. SiRNA NOX4 Interference prevented HKMT-Induced collagen synthesis and increased the expression of miRNA-148. Overexpression of miR-148 suppressed HKMT-induced collagen-1 synthesis and epithelial mesenchymal transition in PMC cells. Conclusions: Our data indicate that NOX4 has the inhibitory effect on the level of mRNA-148 and miRNA-148 may protect against tuberculous pleural fibrosis.