Objective <p>To investigate the mechanism of hsa_circ_0075451 in promoting NSCLC proliferation, metastasis, and glycolysis through interaction with RBM4.</p> Methods <p>Cancerous tissues and paracancerous tissues were collected from 53 cases of NSCLC. RT-qPCR or Western blot was performed to detect hsa_circ_0075451 and RBM4. Relevant sequences or plasmids were transfected into NSCLC cell line A549, and the malignant phenotype of NSCLC cells was detected by CCK-8, EdU, AnnexinV-PI double staining assay, and Transwell. Glycolysis was assessed by glucose consumption, lactic acid production, and glycolysis-related proteins. In vivo tumorigenesis assays were performed to investigate hsa_circ_0075451 functions in NSCLC. Mechanistic studies were analyzed to verify the interaction of hsa_circ_0075451 and RBM4.</p> Results <p>Hsa_circ_0075451 levels were elevated in NSCLC, and reducing its expression diminished cell proliferation, metastasis, glycolysis, and tumor expansion. Hsa_circ_0075451 interacted with RBM4. RBM4 down-regulation restricted NSCLC cell proliferation, metastasis, and glycolysis. RBM4 up-regulation opposed the effects of hsa_circ_0075451 knockdown.</p> Conclusion <p>Hsa_circ_0075451 promotes NSCLC proliferation, metastasis and glycolysis by interacting with RBM4.</p>