--- - |2- Abstract Emerging evidence has illustrated the vital roles of long noncoding RNAs (lncRNAs) in human cancers. However, the role of lncRNAs in non‐small cell lung cancer (NSCLC) is still elusive and poorly understood. In the current study, our team conducted extensive experiments to identify the role of long intergenic nonprotein coding (LINC01296) on NSCLC tumorigenesis. The results illustrated that the elevated LINC01296 expression in NSCLC tissue specimens and cell lines were closely correlated with the poor prognosis of patients with NSCLC. Functional studies revealed that LINC01296 knockdown silenced by small interfering RNAs inhibited proliferation, accelerated apoptosis in vitro, and impaired tumor growth in vivo. Mechanical studies showed that INC01296 harbored miR‐598, acting as a microRNA “sponge.” Besides, miR‐598 targeted the 3′‐UTR of Twist1. Interestingly, transcription factor Twist1 could bind with the promoter of INC01296 and activate its transcriptional level. In summary, we conclude that INC01296/miR‐598/Twist1 constitutes a positive feedback loop to promote the tumorigenesis of NSCLC, providing a novel insight and a valuable therapeutic strategy. - Journal of Cellular Physiology, EarlyView.