〔Abstract〕 Objective To explore the effect of Chaihu Shugan San (CSS) containing serum on neuronal apoptosis in induced by tunicamycin of endoplasmic reticulum stress (ERS) model. Methods The NG108-15 neural cells were induced with tetracycline in the experiment, and an ERS cell model was established and divided into 5 groups: model group (10% blank rabbit serum intervention), donepezil hydrochloride table group (10% donepezil hydrochloride table drug serum intervention), 2.5% CSS drug serum (low-dose) group, 5% CSS drug serum (medium dose) group, and 10% CSS drug serum (high-dose) group. At the same time, a normal group was incubated with normal blank serum and not induced by tetracycline. After completing the observations, flow cytometry and fluorescence staining were performed to detect the apoptosis rate of cells in each group. Results The flow cytometry detection results showed that the apoptosis rate of each intervention group was significantly reduced compared to the model group (P ＜ 0.05). At the same time, the apoptosis rate of cells in the high-dose CSS serum containing group was significantly lower than that in the medium-dose and low-dose group (P ＜ 0.05). Combined fluorescence staining also demonstrated that the apoptosis rate of cells in the high-dose CSS serum group was significantly lower than that in the medium-close and low-dose group. Conclusion CSS has a significant protective effect on neuronal damage caused by ERS, and can inhibit neuronal apoptosis in ERS. Its inhibitory effect increases with increasing drug concentration.