Circular RNAs (circRNAs) have recently been considered as key regulators in carcinogenesis. Nevertheless, the study of circRNAs involved in non-small cell lung cancer (NSCLC) remains largely unclear. In this study, we aim to explore the clinical significance, regulatory effect and mechanism of circ-FOXM1 in NSCLC. The results indicated that circ-FOXM1 overexpression was observed in NSCLC tissues and closely associated with lymph node invasion, higher TNM stage, and unfavorable prognosis. Furthermore, knockdown and ectopic expression of circ-FOXM1 significantly inhibited and promoted the growth, migration and invasion of NSCLC cells, respectively. Mechanistically, miR-1304-5p was discovered as a direct target of circ-FOXM1. Circ-FOXM1 upregulated the level of pancreatic progenitor cell differentiation and proliferation factor (PPDPF) and metastasis-associated in colon cancer 1 (MACC1) by sponging miR-1304-5p, thereby increasing the proliferation and invasion of NSCLC cells. Taken together, this work revealed that circ-FOXM1/miR-1304-5p/PPDPF/MACC1 signaling was essential for the development and progression of NSCLC. (C) 2019 Elsevier Inc. All rights reserved.