Ketamine is a widely used intravenous anesthetic; however, basic and clinical studies have demonstrated that prolonged exposure can cause irreversible injury to the immature human brain. Yes‑associated protein (YAP) is the main effector of the Hippo signaling pathway, which serves an important role in regulating tissue homeostasis and organ size during development. However, whether YAP mediates ketamine‑induced apoptosis is not completely understood. Based on the functions of YAP during apoptosis resistance and cell self‑renewal regulation, the present study hypothesized that YAP serves a role during ketamine‑induced apoptosis. An in vitro model was utilized to investigate the effects of ketamine on neurotoxicity and to further investigate the role of YAP in ketamine‑induced apoptosis using techniques including CCK‑8 assay, flow cytometry and western blotting. The present study assessed the effects of YAP overexpression and knockdown on the expression of typical apoptotic markers in SH‑SY5Y cells. Ketamine induced apoptosis in a dose‑dependent manner, which was regulated by YAP. Following YAP overexpression, ketamine‑treated SH‑SY5Y cells displayed increased activity and viability, whereas expression levels of the apoptotic markers were decreased compared with the negative control group. By contrast, ketamine‑induced apoptosis was enhanced following YAP knockdown. Collectively, the results of the present study indicated that YAP may serve an important role during ketamine‑induced neurotoxicity, and alterations to YAP signaling may counteract ketamine‑induced apoptosis. The neuroprotective effect of YAP activation may serve as a novel pharmacological target for the treatment of ketamine‑induced neurotoxicity via neurogenesis normalization.