Circular RNAs (circRNAs) is a class of non-coding RNA with important functions in tumor development and progression. In the previous study, circ_0020123 was found to be an elevated circRNA in non-small cell lung cancer (NSCLC) tissues screened by high-throughput sequencing. In the current work, we uncovered the clinical significance, biological functions and mechanism of circ_0020123 in NSCLC. The expression profile of circ_0020123 was measured by RT-qPCR. Correlations between circ_0020123 expression and patients' clinical features were evaluated. Cell viability, apoptosis, migration and invasion were detected by cell counting kit-8 (CCK-8), flow cytometric and transwell assay, respectively. Bioinformatics database and luciferase reporter gene assays were utilized to identify the mechanisms of circ_0020123. The results revealed elevation of circ_0020123 in tissue specimens and cells than the nontumorous tissues and 16HBE, separately. The enhancement of circ_0020123 in tumor tissues correlated with positive lymph node metastasis, advanced TNM stages, and adverse prognosis for NSCLC patients. Functionally, silencing of circ_0020123 distinctly suppressed the growth, migration and invasion and inhibited the apoptosis of A549 cells. On the contrary, when circ_0020123 expression was ectopically expressed, the above effects were significantly strengthened in H1299 cell line. For the mechanism exploration, circ_0020123 could sponge miR-488-3p to release its inhibition on ADAM9 expression. Moreover, the functional role of circ_0020123 is partly dependent on its regulation of ADAM9 proved by rescue assays. Taken together, our findings provide the possibility that circ_0020123 may be a new target for NSCLC prognosis prediction and therapy. (C) 2019 Elsevier Inc. All rights reserved.