Human bone marrow mesenchymal stromal cells induce tumour expression of sphingosine-1-phosphate receptor-1 (S1PR1), leading to their resistance to chemotherapy. Targeting S1PR1 by shRNA markedly enhances etoposide-induced apoptosis in neuroblastoma (NB) cells, while overexpression of S1PR1 significantly protects NB cells from multidrug-induced apoptosis via activating JAK-STAT3 signalling. Treatment with FTY720, an FDA-approved drug and antagonist of S1PR1, dramatically sensitizes drug-resistant NB cells to etoposide in in vitro and human neuroblastoma xenograft models. Here, S1PR1 is linked to neoplasm.