Tetrandrine (TET), a bis-benzylisoquinoline alkaloid, shows cytotoxicity against several different types of tumors. However, the mechanism by which TET exerts its anti-cancer capabilities remains unclear. In this study, we confirmed that TET inhibits proliferation and induces apoptosis in neuroblastoma (NB) in vitro and in vivo. Moreover, we revealed that the anti-cancer ability of TET is associated with a decreased expression of anti-apoptotic Bcl-2. Importantly, we demonstrated that the Hippo/YAP pathway is involved in down-regulating of Bcl-2. Notably, YAP overexpression promoted proliferation and suppressed apoptosis, even partially reversed TET-induced effects in NB cells. Our findings support the prospect that TET could be a potential therapeutic agent for NB, and suggest that targeting the Hippo/YAP pathway may represent a valuable approach to NB treatment. (C) 2019 The Authors. Published by Elsevier Inc.