Ghrelin is a multi-functional peptide, its role on cancer cell apoptosis remains controversial. The present study examined the effects and mechanisms of ghrelin on cisplatin-induced apoptosis in human breast cancer cells. It was identified that ghrelin inhibited apoptosis in MDA-MB-231 cells in vitro and reversed the expression of B-cell lymphoma 2 (Bcl2) and Bcl2-associated X, and cleaved caspase-3 induced by cisplatin. Furthermore, ghrelin activated the phosphoinositide 3-kinases/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway after cisplatin treatment. The effects of ghrelin on the cisplatin-induced apoptosis and PI3K/Akt/mTOR signaling were reversed by the growth hormone secretagogue receptor small interfering RNA. The present study suggests that ghrelin may serve as a novel target for cisplatin resistance and a potential indicator of cisplatin sensitivity in breast cancer treatment.