Although many studies had shown that berberine against lung adenocarcinoma mainly focused on different cell signaling pathways, including Sin3A/TOP2B (Chen et al., 2020), Bcl-2/Bax (Li et al., 2018), mTOR (Kumar et al., 2020) and NF-κB/COX-2, Akt/ERK (Lu et al., 2016), miR-19a/TF/MAPK (Chen et al., 2019), etc. It was not clear whether berberine could exert anticancer effect by interfering with DNA replication, the basic process of lung adenocarcinoma cell proliferation. The gene discussed is SIN3A; the disease is lung adenocarcinoma.