This study, for the first time, uncovers the pathogenic roles of Rnd3 in NSCLC, including the following: 1) Rnd3 is down-regulated in A520, H358 and A549, three lung cancer cell lines; 2) forced expression of Rnd3 in A520 and A358 cells inhibits cell proliferation; 3) the Rnd3-mediated cell proliferation is regulated through Notch signaling regulation via post-translational modification. This evidence concerns the gene RND3 and non-small cell lung carcinoma.