Long non?coding RNA Fer?1?like protein?4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression and apoptosis. However, its clinical significance and biological role in non?small cell lung cancer (NSCLC) are completely unknown. The purpose of this study was to investigate the expression of lncRNA FER1L4 in plasma and tissues of patients with NSCLC and study the mechanism of proliferation and apoptosis of lung cancer cells. The expression levels of FER1L4 in plasma and tissues of NSCLC patients and cell lines were analyzed via RT?qPCR. The effects of FER1L4 on cell proliferation, migration and invasion were analyzed by CCK?8, wound healing and Transwell assays, respectively. The expression levels of related proteins were detected by western blot assay, while cell apoptosis was determined by Hoechst staining and flow cytometry. The results revealed that FER1L4 was significantly downregulated in NSCLC plasma and tissues and lung cancer cell lines compared to corresponding controls. Moreover, a significant decrease of cell proliferation, migration and invasion were observed in FER1L4?overexpressed cells. FER1L4 could promote phosphatase and tension homolog deleted on chromosome ten (PTEN) and p53 expression, inhibit AKT phosphorylation expression, thus increasing the proportion of apoptotic cells. The present study indicated that FER1L4 may inhibit cell proliferation and promote apoptosis of NSCLC cells via the PTEN/AKT/p53 pathway, which provides a better understanding of the pathogenesis of NSCLC and may provide a novel potential therapeutic target for clinical treatment.