The depletion of lncRNA MEG8 reduced NSCLC cell proliferation, migration, and invasion by targeting miR-15a/b-5p in vitro. LncRNA MEG8 contributed to tumor growth of NSCLC via miR-15a/b-5p/PSAT1 axis in vivo. These data present a novel function of lncRNA MEG8 in the NSCLC progression, providing valuable evidence for the fundamental role of lncRNAs in the development of NSCLC. This evidence concerns the gene PSAT1 and neoplasm.