Therefore, in this study, we focused on the anticancer effect of Lentinan (LNT for short) against breast cancers and the possible mechanism by using confocal microscopy, Western blotting, histology and immunohistochemistry, immunofluorescence, flow cytometry, etc. Consequently, LNT showed remarkable anti-proliferation effect against ER+ breast cancer cells in vitro and in nude mice. This evidence concerns the gene ESR1 and breast cancer.