Considering SIRT6 inhibition regulates Nrf2 expression in transformed cells, herein, we evaluate the effect of SIRT6 inhibition using Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate on the Nrf2/Keap1 signaling pathway in NSCLC cell lines. The gene discussed is NFE2L2; the disease is non-small cell lung carcinoma.