The microRNAs represent a class of noncoding RNAs with short length and play diverse roles in many biological processes. Despite tremendous effects have been devoted, the role of miR-635 in non-small cell lung cancer (NSCLC) remains elusive. Here we report a potential tumor suppressive function of miR-635 in NSCLC. By microRNA screening based on invasion assays, we identified series of functional miRNAs. The miR-635 was then identified as a potent inhibitor of cell invasion and differentially expressed in normal and cancerous tissues. We further confirmed that Ying Yang 1 (YY1) may be the direct target of miR-635 as miR-635 transfection can significantly decrease endogenous YY1 expression which can mimic the effect of siRNA-mediated YY1 knockdown. Meanwhile, both miR-635 transfection and YY1 silencing can attenuate NSCLC cell invasion. In addition, miR-635 transfection can also significantly inhibit the growth of xenograft tumors. Taken together, our results have suggested a novel tumor suppressive role for miR-635 in NSCLC.