Increasing studies have well-documented the involvement of numerous lncRNAs in regulating the malignant phenotypes of various tumors including non-small cell lung cancer (NSCLC) cells. However, up to date, the effects and mechanism of lncRNA amine oxidase, copper containing 4, pseudogene (AOC4P) in NSCLC progression remain undefined. AOC4P expression in NSCLC cells was detected by qRT-PCR. The protein levels of Wnt/β-catenin pathway-related proteins, matrix metallopeptidase (MMP)-2, and MMP-9 were examined by Western blot. The effects of AOC4P or combined with Wnt agonist BML-284 on the malignant phenotypes in NSCLC cells were explored by CCK-8, Transwell invasion assay, flow cytometry analysis and caspase-3/7 activity. AOC4P was lowly expressed in NSCLC samples and cells. Overexpression of AOC4P inhibited viability, the expression of MMP-2 and MMP-9, and invasion of NSCLC cells. Apoptosis and caspase-3/7 activity were suppressed in response to AOC4P overexpression in NSCLC cells. AOC4P overexpression suppressed tumor growth in a xenograft mouse model. Activation of the Wnt/β-catenin pathway by BML-284 abolished the effects of AOC4P overexpression on cell viability, invasion and apoptosis in NSCLC cells. In conclusion, AOC4P overexpression suppresses viability and invasion and induces apoptosis in NSCLC cells via inhibition of the Wnt/β-catenin pathway.Copyright © 2020. Published by Elsevier B.V.