Smad signalling plays an important role in the neurobiology, which can be induced by bone morphogenetic protein 2 (BMP2) and be regulated by endocytosis. However, it is still unclear whether endocytosis regulates BMP2-Smad-mediated proliferation and neurite growth in SH-SY5Y. Here we investigated the effects of endocytosis on BMP2-mediated Smad signallings using the neuroblastoma SH-SY5Y cell. In this study, using dynasore, dynamin-dependent endocytosis was assayed; using Western blot and neurite outgrowth assay, BMP2-Smad signalling and SH-SY5Y neurite outgrowth were measured. In the present study, our data showed that dynasore indeed inhibited dynamin-dependent endocytosis in SH-SY5Y. The Smad 1/5/8 phosphorylation level was upregulated in response to exogenous BMP2, while BMP2-induced p-Smad 1/5/8 expression was significantly suppressed due to BMP2 and dynasore co-treatment (p < 0.001). In addition, the immunocytochemical staining revealed high nuclear expression of p-Smad 1/5/8 in response to BMP2 induction, whereas BMP2 and dynasore reduced BMP2-induced p-Smad 1/5/8 expression (p < 0.001). Besides, BMP2-induced SH-SY5Y proliferation and neurite outgrowth were effectively affected by the inhibition of dynamin-dependent endocytosis. In conclusion, dynamin-dependent endocytosis regulates BMP2-Smad signalling in the SH-SY5Y cells and further interferes with the proliferation and neurite outgrowth of SH-SH5Y, which offers a new therapeutic prospect for the neuroblastoma.