Circular RNAs (circRNAs) have been demonstrated as potential biomarkers for the diagnosis and treatment of human diseases. Previous studies have unveiled the carcinogenic role of circRNA_102399 (circCNN2) in lung cancer. Through the UALCAN database, it was found that CNN2, the parent gene of circCNN2, was specifically highly expressed in human lung squamous cell carcinoma (LUSC) cells, but the regulatory mechanism of circCNN2 in LUSC is unclear. In this study, circCNN2 expression in LUSC cells was examined via RT-qPCR, and its effects on LUSC progression was verified through functional assays. The subcellular localization of circCNN2 was identified via FISH assay, and the underlying mechanism of circCNN2 on the activation of MAPK signaling pathway was determined through mechanism experiments. Results demonstrated that circCNN2 was upregulated in LUSC cells, and it promoted LUSC cell proliferation and invasion. Besides, circCNN2 acted as a competing endogenous RNA (ceRNA) to sponge miR-184 to upregulate E2F transcription factor 1 (E2F1) expression. Furthermore, it was verified that circCNN2 activated the generic mitogen-activated protein kinases (MAPK) signaling pathway through E2F1 and thus promoting LUSC progression. In a word, this study indicated that circCNN2 activated MAPK signaling pathway through the miR-184/E2F1 axis to promote proliferation and invasion of LUSC cells.