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Guosheng Xiong,1,* Liyin Li,2,* Xiaobo Chen,1 Sinuo Song,3 Yunping Zhao,1 Wenke Cai,4 Jingping Peng4 1Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, People’s Republic of China; 3Department of Medical Management, Kunming General Hospital, Kunming, Yunnan 650032, People’s Republic of China; 4Department of Cardiovascular and Thoracic, Kunming General Hospital, Kunming, Yunnan 650032, People’s Republic of China *These authors contributed equally to this work Aim: The purpose of this study is to consider the function of cytoskeleton-associated protein 2-like (CKAP2L) in lung adenocarcinoma (LAD) development and its prognostic value. Methods: The mRNA expression of CKAP2L and its correlation with clinical factors in LAD patients were analyzed from the data taken from The Cancer Genome Atlas and The First Affiliated Hospital of Kunming Medical University. We constructed H460 and A549 cell lines with silenced CKAP2L using RNA interference. Cell counting kit-8 assay and colony formation assays were carried out to determine the function of CKAP2L in H460 and A549 cell proliferation. Transwell and wound healing assays were applied to determine the effect of CKAP2L on H460 and A549 cell invasion and migration. The influences of CKAP2L on mitogen-activated protein kinase signaling pathway-related proteins were tested by Western blotting. Results: CKAP2L expression is enhanced in LAD tissues and is predictive of poor prognosis in LAD patients. High expression of CKAP2L is associated with stage (P<0.001), lymph node status (P=0.002), and metastasis (P=0.025). Depletion of CKAP2L dramatically suppressed the proliferation, migration, and invasion of H460 and A549 cells. Moreover, the ratio of p-MEK/MEK and p-ERK/ERK reduced obviou