The circular RNA (circRNA) circEPSTI1 has been recently identified as a new cancer-associated circRNA in multiple types of cancer. However, the involvement of circEPSTI1 in non-small cell lung cancer (NSCLC) remains unexplored. The purpose of this study was to explore the expression pattern and function of circEPSTI1 in NSCLC. We found that circEPSTI1 expression was significantly elevated in NSCLC. In vitro experiments elucidated that knockdown of circEPSTI1 caused a significant reduction in NSCLC cell proliferation and invasion. Moreover, circEPSTI1 was identified as an miRNA sponge of miRNA-1248. Knockdown of circEPSTI1 markedly increased the expression of miR-1248 in NSCLC cells. Upregulation of miR-1248 significantly restricted the proliferation and invasion of NSCLC cells. Inhibition of miR-1248 promoted the proliferation and invasion of NSCLC cells and blocked the circEPSTI1 knockdown-mediated inhibitory effect on NSCLC cell proliferation and invasion. Subsequent data revealed that the tumor-promoting gene tripartite motif-containing protein 24 (TRIM24) is a target gene of miR-1248. The upregulation of TRIM24 partially reversed circEPSTI1 knockdown-or miR-1248 overexpression-induced tumor suppressive effect in NSCLC cells. In summary, our data demonstrate that downregulation of circEPSTI1 represses the proliferation and invasion of NSCLC by inhibiting TRIM24 via miR-1248 upregulation. (C) 2020 Elsevier Inc. All rights reserved.