Bryonia multiflora, one of the species of Bryonia L. (Cucurbitaceae) genus, is a perennial, dioecious, herbaceous plant with rhizome-shaped roots. Bryonia species have anti-inflammatory, antimicrobial, cytotoxic, antioxidant, etc., activities and their components consume antitumoral effects. Purpose of the study to investigate the effect of Bryonia Multiflora extract (BMST) on breast cancer cells. Our results revealed that MCF-7 and MDA-MB-231 cells underwent significant morphological changes leading to cell rounding. No significant changes were observed in the cell viability by MTT. Acridine orange staining of our cells gave rise to think that BMST might lead our cells to autophagy. Therefore, possible molecular mechanisms underlying morphological changes such as autophagy (LC-3B, Beclin, AMBRA1) and apoptosis (Bcl-2) were evaluated on mRNA and protein levels. BMST treated MCF-7 and MDA-MB-231 cells had increased levels of autophagy markers whereas decreased levels of Bcl-2. p21 levels were also found to be increased in both cells. Analysis of lncRNA expressions has shown that BMST treatment led to changes in the expression levels of several lncRNAs playing roles in autophagy. The current study has shown that BMST induces autophagy in MCF-7 and MDA-MB-231 cells via regulating the lncRNAs revealing that BMST could be a promising therapeutic agent.