Update publication information. Epithelial cells arrested in G2/M phase of the cell cycle after injury is a key checkpoint for determining the wound-healing to either normal cell proliferation or fibrosis. The mechanism that regulates the fibrogenic response after injury is not well understood. Here, we identified a kidney- and liver-enriched circular RNA, circBNC2, which was abundantly expressed in normal renal tubular cells and hepatocytes but significantly downregulated after acute ischemic or toxic insults. The loss of circBNC2 was at least partially mediated by upregulation of DHX9. Gain-of- and loss-of-function studies, both in vitro and in vivo, demonstrated that circBNC2 acted as a negative regulator for cell G2/M arrest by encoding a novel protein that promoted formation of CDK1/cyclin B1 complex. Restoring circBNC2 in experimentally-induced fibrotic kidney and liver decreased G2/M arrested cells with secretion of fibrotic factors, mitigated extracellular matrix deposition and fibrosis. Decreased expression of circBNC2 and increasement of G2/M arrest of epithelial cells were recapitulated in human IRI-induced chronic kidney disease and inflammation-induced liver fibrosis, highlighting the clinical relevance. These findings suggest that preventing the fibrogenic response by regulating cell cycle arrest might be a potential therapeutic strategy for organ fibrosis.