Overall, although the effects of CHIR99021 and the combined application of CHIR99021 and Notch3-shRNA on the cell proliferation and apoptosis aren’t completely similar in the three cell lines, our findings still indicate that Notch3 signaling can be activated by canonical Wnt signaling and a functional link between Wnt and Notch signaling pathways exists in NSCLC, at least, which partially is associated with their regulations on the expressions of cyclinA and caspase-3. Here, NOTCH3 is linked to non-small cell lung carcinoma.