Background/Aims: The transcription factor CCAAT/enhancer-binding protein a (C/EBP alpha) is a basic leucine zipper transcription factor that plays essential roles in tumor progression. Although decreased or absent C/EBP alpha expression in many cancers suggests a possible role for C/EBP alpha as a tumor suppressor, the functions of C/EBP alpha in lung adenocarcinoma remain unclear. Methods: Here, C/EBP alpha expression levels in 26 lung adenocarcinoma and para-carcinoma tissue samples were detected by qRT-PCR and immunohistochemistry. Cell transwell assays, wound healing assay and three-dimensional spheroid invasion assay were performed to assess the effects of C/EBP alpha on migration and invasion in lung adenocarcinoma cells in vitro. Western blotting was applied to analyze the potential mechanisms. Results: C/EBPa was found to be decreased in lung adenocarcinoma tissues compared to para-carcinoma tissues. Overexpression of C/EBP alpha significantly inhibited the migration and invasion of lung adenocarcinoma cells. In addition, C/EBP alpha overexpression suppressed the epithelial-mesenchymal transition (EMT) that was characterized by a gain of epithelial and loss of mesenchymal markers. Further study showed that C/EBP alpha suppressed the transcription of beta-catenin and downregulated the levels of its downstream targets. Conclusion: Our data suggest that C/EBP alpha inhibits lung adenocarcinoma cell invasion and migration by suppressing beta-catenin-mediated EMT in vitro. Thus, C/EBP alpha may be helpful as a potential target for treatment of lung adenocarcinoma. (C) 2017 The Author(s) Published by S. Karger AG, Basel