There are only a few scientifically robust mechanistic studies with Lycium fruits, also known as Goji berry, that have addressed preventive or therapeutic intervention of breast cancer. In the present study, we aim to investigate the antiproliferative effects of both Lycium barbarum fruit (Goji berry red fruit) and Lycium ruthenicum (Goji berry black fruit) extracts against triple-negative MDA-MB-231 cells and explore the possible mechanisms of their anticancer effects. IC(50 )values were 87.0 and 79.4 mu g/mL for goji berry black fruit extract and goji berry red fruit extract, respectively. Pretreatment with both extracts inhibited phosphorylation of epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinases (ERK) in epidermal growth factor-treated MDAMB-231 cells. The present study also examined whether the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway was involved in the regulation of Goji berry extract-induced cell death. Furthermore, treatment with Goji berry fruit extracts inhibited the expression of anti-apoptotic Bcl-2, but enhanced pro-apoptotic Bax expression at transcriptional levels and induced cancer cell apoptosis by activation of pro-apoptotic caspase-9 and caspase 3. Goji berry fruit extracts caused death of MDA-MB-231 breast cancer cells by inhibiting EGFR/ERK-mitogen activated protein kinases (MAPK) and PI3K/Akt signaling pathways. This study suggests that Goji berry fruit extracts might be beneficial for treating triple-negative breast cancer.