Epithelial-to-mesenchymal transition (EMT) of epithelium and airway epithelial cell proliferation disorder are key events in idiopathic pulmonary fibrosis (IPF) pathogenesis. During EMT, epithelial cell adhesion molecules (EpCAM, such as E-cadherin) are downregulated, cytokeratin cytoskeletal transforms into vimentin-based cytoskeleton, and the epithelial cells acquire mesenchymal morphology. In the present study, we show abnormal upregulation of tumor protein p63 (TP63) and downregulation of miR-184 in IPF. Transforming growth factor beta 1 (TGF-β1) stimulation of BEAS-2B and A549 cell lines significantly increased the protein levels of Tp63, alpha-smooth muscle actin (α-SMA), and vimentin, but decreased EpCAM protein levels, and promoted viability of both BEAS-2B and A549 cell lines. TP63 knockdown in BEAS-2B and A549 cell lines significantly attenuated above-described TGF-β1-induced fibrotic changes. miR-184 targeted TP63 3'-UTR to inhibit Tp63 expression. miR-184 overexpression within BEAS-2B and A549 cell lines also attenuated TGF-β1-induced fibrotic changes. miR-184 overexpression attenuated bleomycin-induced pulmonary fibrosis in mice. Moreover, TP63 overexpression aggravated TGF-β1-stimulated fibrotic alterations within BEAS-2B and A549 cells and significantly reversed the effects of miR-184 overexpression, indicating miR-184 relieves TGF-β1-stimulated fibrotic alterations within BEAS-2B and A549 cells by targeting TP63, while TP63 overexpression reversed miR-184 cellular functions. In conclusion, the miR-184/TP63 axis modulates the TGF-β1-induced fibrotic alterations in epithelial cell lines and bleomycin-induced pulmonary fibrosis in mice. Therefore, these results confirm that the miR-184/TP63 axis is involved in IPF progression.