Excessive　exposure　to　commonly　used　anesthetic　agents,　such　as　ketamine,　may　induce　permanent　damage　to　immature　human　brains.　In　this　work,　we　used　a　human　embryonic　stem　cell　(hESC)-derived　neuron　model　to　assess　the　expression　and　function　of　human　microRNA　735　(hsa-miR-375)　in　regulating　ketamine-induced　neural　cell　death　and　neural　toxicity　in　vitro.　In　the　in　vitro　culture,　hESC-derived　neurons　were　incubated　with　ketamine　for　72　h.　After　that,　cell　viability,　reactive　oxygen　species　activity,　neural　apoptosis,　neurite　degeneration,　and　hsa-miR-375　gene　expression　were　assessed,　respectively.　We　found　ketamine　induced　neural　death,　reactive　oxygen　species　augmentation,　neural　apoptosis,　neurite　degeneration　and　hsa-miR-375　upregulation,　in　hESC-derived　neurons.　In　addition,　we　discovered　that,　lentivirus-mediated　mR-375　downregulation　protected　ketamine-induced　neural　cell　death　and　neural　toxicity.　Also,　human　brain　derived　neurotrophic　factor　(BDNF)　was　found　to　be　directly　and　reversely　regulated　by　hsa-miR-375.　Moreover,　BDNF　downregulation　was　shown　to　functionally　reverse　the　protective　effect　of　miR-375　downregulation　on　ketamine-induced　neural　cell　death　and　neural　toxicity.　Overall,　this　work　provided　strong　evidence　showing　hsa-miR-375　is　an　active　regulator　in　anesthesia-induced　neural　cell　death　and　neural　toxicity,　possibly　via　inverse　regulation　on　BDNF　gene.