Herein, we report that the nicotinamide adenine dinucleotide 1 (NAD1)-dependent deacetylase SIRT1 can function as an intrinsic negative modulator of Delta-like ligand 4 (DLL4)/Notch signaling in Lewis lung carcinoma (LLC) xenograft-derived vascular endothelial cells (lung cancer-derived ECs). Here, SIRT1 is linked to lung cancer.