Non-small cell lung cancer (NSCLC) is the major cause of cancer-associated death worldwide, but its underlying mechanisms remain to be fully elucidated. Long noncoding RNAs (lncRNAs) are known to play an important role in the aberrant regulation of gene expression in many cancers, including NSCLC. Here, we investigated the involvement of the lncRNA KTN1-AS1 in NSCLC. We found that KTN1-AS1 expression was upregulated in NSCLC tissue and was positively associated with poor prognosis. KTN1-AS1 knockdown inhibited cell growth and proliferation, increased apoptosis, and modulated the expression of cell cycle- and apoptosis-related proteins (cyclin A1, cyclin-dependent kinase 2, Bcl2, and Bax) in NSCLC cell lines and tumour xenografts in nude mice. KTN1-AS1 bound to and directly regulated the expression of miR-130a-5p. Notably, miR-130a-5p overexpression suppressed NSCLC cell proliferation and increased apoptosis in vitro and in vivo, and this effect was reversed by KTN1-AS1 overexpression. Finally, we showed that KTN1-AS1 modulated the expression of 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a miR-130a-5p target and key regulator of autophagy in NSCLC cells. Taken together, our results suggest that the KTN1-AS1/miR-130a-5p/PDPK1 pathway may be a potential therapeutic target for NSCLC.