Monascus-fermented red mold rice (RMR) extracts have recently been proved to possess anticancer activities, but the anticancer effect of breast cancer cells treated with RMR is not yet well understood. In an effort to identify proteins that may be involved in RMR-induced breast cancer cell death, we employed proteomic analysis coupled with LC-nanoESI-MS/MS on MCF-7 cells exposed to two RMR extracts, ethyl acetate extract (EAE) and ethanol extract (EE). Sixupregulated proteins were identified in EAE-induced MCF-7 cells, including glyceraldehyde-3-phosphate dehydrogenase, pyruvate dehydrogenase E1 component, heat shock 27 kDa protein 1, cathepsin D, protein disulphideisomerase A3, and prohibitin. The upregulated expression of other 4 proteins was seen in EE-induced MCF-7 cells, including alloalbuminvenezia, annexin A5, endoplasmic reticulum protein 29 isoform 1 precursor, and cellular retinoic acid binding protein 2. The same two down-regulated proteins were identified on cells after treatment with both extracts, dermcidin preproprotein and poly(rC) binding protein 1. These proteins have been implicated in proapoptotic regulation, stress modulation, tumor suppression, and survival factor activity. These analysescould provide valuable information for further exploration of RMR as a promising chemopreventive agent against breast cancer.