Coptidis Rhizoma (Huang Lian) is an ancient traditional Chinese herb, mainly used for heat-clearingand detoxicating. In recent years, many pharmacological experiments showed that the extract and active ingredients have anti-bacteria, anti-cardiovascular diseases, lipid-lowering and anti-tumor activities. Berberine is one of the main active ingredients, which is an isoquinoline alkaloid. In addition to widely used in the treatment of gastrointestinal disorders, it also has a wide range of physiological functions like neuroprotective, hyperlipidemia remedy, etc. In the field of anti-cancer research, berberine obtained a wealth of research results. The main mechanism of berberine of the antitumor effect is to inhibit tumor cell proliferation, induce apoptosis, regulategene expression, and inhibit oxidation. To survive and reproduce in harsh competitive environments, organisms have developed molecular mechanisms to respond adaptively to various hazards or “stressors” that they encounter. These stressors include different chemicals and energy changed. In most cases, the response of the cell or organism to the stressor exhibits a biphasic dose response, with beneficial/adaptive responses at low doses and adverse/destructive effects at high doses. Therefore, a term HORMESIS was given to indicate this phenomenon, as defined “a process in which exposure to a low dose of a chemical agent or environmental factor that is damaging at higher doses induces an adaptive beneficial effect on the cell or organism”. By now, this phenomenon is widely acknowledged in various fields. Our experiments found that coptis crude extract and its major active constituent berberine at high doses strongly inhibited the growth of tested tumor cells, while the low dose groups were observed to significantly stimulate the growth of tumor cells, indicating an obvious hermetic effect I induced by coptis extracts. XTT colorimetric assays showed that coptis crude extract and berberine can stimulate the growth of B16, MCF-7, MDA-MB-231 cells at low doses,except A549 cells, while the agents at high dosesdose-dependently decreased the cell viability ofall tumor cells. Afterintragastric administration ofcoptis crude extractat low and high doses to micewith subcutaneous transplantation of B16-F10 melanoma, tumor growth curves and tumor weight also showeda biphasic effect, which is the typical appearance of hormesis. Through combinational treatment of coptis crude extract and berberine with known anti-cancer chemotherapeutic drugs on cancer cell lines, we found that coptis extracts at low doses significantly reduced the anticancer activities of chemotherapy drugs. Interestingly, we found that the effects of coptis extracts on the intracellular levels of reactive oxygen species and expression levels of cell growth/death genes also showed hermetic phenomenon, suggesting the underlying mechanisms of hermetic effects, at least induced by coptis extracts. Western blot results suggest thesustained phosphorylation of ERK and STAT3 gene may be the cause of tumor cell proliferation stimulated by low-dose coptis extract and berberine.The hermetic effects of coptis extracts on breast cancer cells were, to some extent, related to the status of estrogen receptor (ER) and the relevant pathways, as evidenced that ER antagonist and siRNA significantly attenuated the hermetic effects of coptis extracts in MCF-7 cells, an ER positive cell line, but not in MDA-MB-231 cells, an ER negative cell line. In summary, this study shows that coptiscrude extract and berberine exhibit typical hermetic effects on various cancer cells in vitro and in vivo, shedding light on the mechanisms of traditional Chinese medicine from new angles of view, and practically, suggesting more attention should be paid to the application of coptis extracts in clinic, in particularly, in combination with other drugs in cancer treatment.