Hypoxia plays an important role in the development of renal fibrosis. G/M arrest in renal tubular cells is an important pathway in the development of chronic kidney disease. It is unknown whether hypoxia leads to renal fibrosis via the regulation of G/M arrest in renal tubular epithelial cells. For the first time, to our knowledge, we showed that hypoxia induces G/M arrest in renal tubular cells leading to renal fibrosis, and microRNA are involved in this regulation. We compared microRNA expression between hypoxia and normoxia in HK2 cells and found miR-493 to be highly expressed at 24 and 48 h after hypoxia. The overexpression of miR-493 reduced the expression of the cell cycle regulator, Stathmin (STMN)-1, and increased the percentage of G/M phase cells and profibrotic factors in HK2 cells. Targeting STMN-1 with short hairpin RNA produced an effect similar to that of miR-493 overexpression. On contrast, the miR-493 inhibitor reversed these effects in vitro. Consistent with these results, miR-493 sponge adeno-associated virus reduced the expression of profibrotic factors and increased STMN-1 in vivo. In summary, these results suggest that the miR-493-STMN-1 pathway contributes to hypoxia-induced tubular epithelial cell G/M arrest and renal fibrosis. Abrogating G/M arrest and blocking the miR-493-STMN-1 pathway will provide further insight for the development of antifibrosis therapy.-Liu, T., Liu, L., Liu, M., Du, R., Dang, Y., Bai, M., Zhang, L., Ma, F., Yang, X., Ning, X., Sun, S. microRNA-493 targets STMN-1 and promotes hypoxia-induced epithelial cell cycle arrest In G/M and renal fibrosis.