Non-small cell lung cancer (NSCLC) is a highly malignant tumor. Many circular RNAs (circRNAs) are reportedly in regulating the progression of NSCLC. To identify potential therapeutic targets for NSCLC, we conducted a bioinformatics analysis of circRNAs differentially expressed between NSCLC tissues and adjacent normal tissues. Hsa_circ_0007580 was upregulated in NSCLC tumor tissues, and the expression of its host gene (protein kinase Ca) correlated negatively with overall survival. Short-hairpin RNAs were used to knock down hsa_circ_0007580 in NSCLC cells, and gene and protein levels were measured with qRT-PCR and Western blotting, respectively. NSCLC cell proliferation, migration and apoptosis were evaluated with CCK-8 assays, Ki-67 staining, Transwell assays and flow cytometry, respectively. Knocking down hsa_circ_0007580 inhibited proliferation and invasion by NSCLC cells and induced their apoptosis. Dual luciferase reporter assays indicated that miR-545-3p can bind to hsa_circ_0007580 (suggesting that hsa_circ_0007580 sponges miR-545-3p) and to protein kinase Ca (suggesting that miR-545-3p directly inhibits this gene). In a xenograft tumor model, downregulating hsa_circ_0007580 inhibited NSCLC tumorigenesis by inactivating p38/mitogen-activated protein kinase signaling. Thus, silencing hsa_circ_0007580 notably inhibited NSCLC progression and , suggesting this circRNA could be a novel treatment target for NSCLC.