〔Abstract〕 Objective To investigate the effect of modified hyaluronic acid(HA) hydrogel-controlled release brain-derived neurotrophic factor(BDNF) on the growth, differentiation, and apoptosis of rat embryonic neural stem cells(rFNSCs). Methods The experiment took rat embryonic stem cells as the research object. The experiments were divided into three groups, blank control group [rFNSCs co-cultured with poly(lactic-co-glycolic acid)(PLGA)and HA],conditional control group(rFNSCs co-cultured with BDNF-PLGA and HA), and experimental group(rFNSCs co-cultured with BDNF-PLGA and modified hyaluronic acid hydrogel that is Dex-HA). ELISA was used for detecting the release curve of BDNF in the controlled-release scaffold. The Live/Dead assay detected the apoptosis of rFNSCs in each group, CCK-8 experiment was used to test the cell proliferation activity of rFNSCs after coculture with hydrogel. The differentiation ratios of rFNSCs in different groups were detected by immunocytochemical staining.Results ELISA result showed that the controlled-release scaffold could release BDNF for 14 days.Live/Dead result showed the number of rFNSCs apoptotic in experimental group was less than blank control group and conditional control group. CCK-8 experiment result showed that the cell proliferation activity of rFNSCs in the experimental group was showed stronger survivability than blank control group and conditional control group. The difference was statistically significant(P<0. 05). Moreover, immunocytochemical staining showed that the experimental group hydrogel could promote the neuronal differentiation of rFNSCs and reduce their differentiation into astrocytes in vitro compared with the blank control group and the conditional control group. The difference was statistically significant(P<0. 05).Conclusion modified hyaluronic acid hydrogel controlled release brain-derived neurotrophic factor can promote the growth and differentiation of rFNSCs and reduce their apoptosis.