Metformin with tenovin‐6 synergistically down‐regulated SIRT1 expression by recruiting HIC1 on the SIRT1 promoter; subsequently, this resulted in accumulation of p53 acetylation and induction of the apoptotic pathway in a functional LKB1‐deficient NSCLC cells. The gene discussed is TP53; the disease is non-small cell lung carcinoma.