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OBJECTIVE To explore the effects of long intergenic non-coding ribonucleic acid 00460 (LINC00460) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS In this study, the expression of LINC00460 in lung cancer tissues and its prognostic potential in NSCLC patients were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) website and the Cancer Genome Atlas (TCGA) database. Then, the influences of silenced LINC00460 on proliferation and apoptosis in A549 cells were observed via methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, and flow cytometry in vitro. Moreover, Dual-Luciferase reporter assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the targeting relationship between LINC00460 and micro RNA (miR)-539. The biological role of the LINC00460/miR-539 axis in the proliferation of A549 cells was examined using MTT assay. RESULTS It was found that the expression level of LINC00460 was significantly upregulated in NSCLC tissues and cell lines, and particularly negatively correlated with the overall survival (OS). According to the in vitro experimental results, LINC00460 knockdown inhibited the proliferation of A549 cells, but promoted their apoptosis. Dual-Luciferase reporter assay results revealed that miR-539 was directly targeted by LINC00460 and involved in the LINC00460-mediated proliferation of A549 cells. CONCLUSIONS LINC00460 is overexpressed in NSCLC tissues and can promote the growth of NSCLC cells by targeting miR-539.