Lysophospholipase1 (LYPLA1) also known as acyl‑protein thioesterase1 (APT1) belongs to the superfamily of α/β hydrolase. It has been found to have the properties of a homodimer by manifesting depalmitoylation as well as lysophospholipase activity. LYPLAs are under the control of both microRNAs, miR‑138 and miR‑424. They were observed to be significantly overexpressed in chronic lymphocytic leukemia cells. To date, LYPLAs are the sole enzymes recognized to activate depalmitoylation. In this study, we provide the expression pattern of LYPLA1 in non‑small cell lung cancer (NSCLC) using four different NSCLC cell lines. Western blot analysis and RT‑PCR were performed to detect the protein expression and mRNA expression of LYPLA1 in NSCLC cell lines. We detected the highest LYPLA1 protein expression level in SPC‑A‑1 cells followed by A549 cells, and the highest LYPLA1 mRNA expression level was detected in the SPC‑A‑1 cells followed by the H1299 cell line. We found that suppression of LYPLA1 expression using small‑interfering RNA significantly inhibited proliferation, migration and invasion of the LYPLA1‑transfected NSCLC cells. Furthermore, we explored the involvement of LYPLA1 in the regulation of epithelial‑mesenchymal transition (EMT). The epithelial marker E‑cadherin was significantly increased, while mesenchymal markers N‑cadherin, vimentin and SNAIL were markedly decreased in the LYPLA1‑silenced cells. Collectively the results of the present study suggest that the LYPLA1 gene plays a tumor‑promotor role in NSCLC cells in vitro.