The transient receptor potential vanilloid 4 (TRPV4) is a highly Ca^2 +-permeable non-selective cation channel in TRPV family. Accumulating evidence hints that TRPV4 play a significant role in a wide diversity of pathologic changes. Fibrosis is a kind of chronic disease which was characterized by the formation of excessive accumulation of extracellular matrix (ECM) components in tissues and organs. In recent years, a growing body of studies showed that TRPV4 acted as a crucial regulator in the progression of fibrosis including myocardial fibrosis, cystic fibrosis, pulmonary fibrosis, hepatic fibrosis and pancreatic fibrosis, suggesting TRPV4 may be a potential therapeutic vehicle in fibrotic diseases. However, the mechanisms by which TRPV4 regulates fibrosis are still undefined. In this review, firstly, we intend to sum up the collective knowledge of TRPV4. Then we provided the latent mechanism between TRPV4 and fibrosis. We also elaborated the distinct signaling pathways focus on TRPV4 with fibrosis. Finally, we discussed its potential as a novel therapeutic target for fibrosis.