Objective    To investigate the expression and biological function of centromere protein F (CENPF) in non-small cell lung cancer (NSCLC) and the association with prognosis. Methods    Through retrieving and analyzing the bioinformatics data such as Oncomine database, Human Protein Atlas (HPA), Kaplan-Meier Plotter, STRING and DAVID database, the expression of CENPF in both normal tissues and cancer tissues of lung cancer patients was identified, and the protein interaction network analysis, functional annotation and pathway analysis of CENPF with its associated genes were carried out. Results    CENPF was overexpressed in lung adenocarcinoma tissues, but not in normal tissues. The median overall survival (OS) of NSCLC patients with low expression of CENPF was significantly longer than that of patients with high expression of CENPF. Further sub-analysis showed that low expression group from lung adenocarcinoma patients had longer median disease-free survival and OS compared with high expression group patients. CENPF and its associated hub genes mainly affected the protein K11-linked ubiquitination in biological process, anaphase-promoting complex (APC) in cell composition, ATP binding in molecular function, and cell cycle in KEGG pathway. Conclusion    CENPF is regulated in tumorigenesis and progression of NSCLC, and its protein expression level has the value of early diagnosis and prognosis evaluation in lung adenocarcinoma. It is suggested that CENPF gene can be a potential target for molecular targeted therapy of NSCLC.