Because we reported previously that HBP1 inhibited tumor growth by up-regulating p16 expression (20), to prevent p16 from interfering, we chose lung cancer cell lines A549 (p16−/−) and H1299 (p16−/− plus p53−/−) (32) as target cells to detect whether HBP1 had a causative role in promoting p21 expression. The gene discussed is HBP1; the disease is lung cancer.