Background <p>Lung squamous cell carcinoma (LUSC) is a prevalent and aggressive subtype of lung cancer. Although LINC01980 has been implicated in the development of several cancers, its specific mechanisms in LUSC remain unclear.</p> Methods <p>Through GEO database analysis, LINC01980 was identified as aberrantly expressed in LUSC. Using LncBook 2.0, we predicted a target relationship between LINC01980 and miR-204-3p. Validation was performed using dual luciferase reporter assay and RNA pull-down experiments. An analysis of LUSC clinical samples and TCGA data revealed differential expressions of LINC01980 and miR-204-3p. The expression levels of these two molecules were quantified by RT-qPCR in both patient tissues and cell lines. To measure cell proliferation, the CCK-8 assay was applied. Apoptosis was evaluated via flow cytometry, whereas cell migration and invasion were investigated using the Transwell assay. Gene knockdown experiments demonstrated that LINC01980 influences malignant phenotypes in vitro by regulating miR-204-3p.</p> Results <p>LINC01980 was abundantly expressed in LUSC tissues and cell lines and significantly enhanced malignant activities including proliferation, migration, and invasion. Furthermore, LINC01980 promotes tumor progression by suppressing miR-204-3p expression. Rescue experiments confirmed that the depletion of miR-204-3p reverses the tumor-suppressive effects caused by LINC01980 knockdown, indicating that the oncogenic function of LINC01980 is dependent on its negative regulation of miR-204-3p.</p> Conclusion <p>LINC01980 drives LUSC invasiveness by targeting miR-204-3p, providing new insights into its tumor-promoting role and underlying mechanisms.</p>