Aberrant expression of miR-15a-5p has been frequently reported in some cancers excluding lung cancer. The role and its molecular mechanism of miR-15a-5p in lung cancer have not been reported. In this study, we explored the effects of miR-15a-5p overexpression on apoptosis and invasion in lung cancer cells. The mRNA level of miR-15a-5p in non-small cell lung cancer (NSCLC) lines was determined by real-time PCR. The miR-15a-5p mimic was transiently transfected into lung cancer cells using Lipofectamine (TM) 2000 reagent. Subsequently, the Brdu-ELISA results showed that introduction of miR-15a-5p inhibited cell proliferation. In addition, miR-15a-5p overexpression could also inhibit EMT of A549 and H460 cells. qRT-PCR were used to determined the expressions of matrix metalloproteinase-2 and -9 (MMP-2 and -9) in lung cancer cells. Next, we found that NF-kappa B1 expression was evidently reduced by up-regulation of miR-15a-5p. Bioinformatics analysis predicted that the NF-kappa B1 was a potential target gene of miR-15a-5p. Luciferase reporter assay further confirmed that miR-15a-5p could directly target the 3' UTR of NF-kappa B1. In conclusion, miR15a-5p suppresses proliferation and metastasis in lung cancer cells by down-regulation of NF-kappa B1 and overexpression of miR-15a-5p might be a potential therapeutic strategy for the treatment of lung cancer in the future.