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Long intergenic nonprotein coding RNA 518 (LINC00518) is recognized to impart cancer proliferation and metastasis in lung adenocarcinoma (LUAD). However, the study about the relationship between LINC00518 and LUAD is shallow so far. In our work, LINC00518 was predicted to be a negative regulator in LUAD based on the TCGA database. It was further verified that the cell proliferation, colony formation, migration, and invasion of LUAD could be obviously inhibited by the knockdown of LINC00518. Moreover, miR-335-3p/CTHRC1 axis was intensively possible to be a critical regulator in the effect of LINC00518 on LUAD via visual ceRNA network. Importantly the progress of LUAD was relevant to the active CTHRC1 which was realized by the target of LINC00518 to miR-335-3p. Furthermore, the knockdown of LINC00518 exhibited a synergistic effect with VS6063, an inhibitor of FAK protein, in the suppression of LUAD indicating that miR-335-3p/CTHRC1 axis was potentially exploitable as a targeted intervention to integrin β3/FAK signal pathway in LUAD. All the collective results demonstrated that LINC00518 could be a promising biomarker of the prognosis of LUAD and possibly a therapeutic target via miR-335-3p/CTHRC1 axis.