〔Abstract〕 Objective To explore whether dendrobium polysaccharide(DOP) can inhibit the apoptosis of nerve cells caused by tumor necrosis factor-α(TNF-α) and the optimal concentration of DOP. Methods Mouse hippocampal neurons(HT22) were cultured with different concentrations of TNF-α to determine the optimal concentration of TNF-α induced HT22 cell apoptosis. After co-cultured with different concentrations of DOP and the optimal concentration of TNF-α for 24 hours, the expression of apoptosis related genes and proteins was detected by PCR and Western blot to find out the inhibition of DOP on HT22 cells. At the same time, the number and proportion of HT22 cells apoptosis were observed by Giemsa staining, Hoechst staining, Tunel staining and flow cytometry. Results Compared with the normal culture group, TNF-α increased the expression of apoptosis related genes in HT22 cells, and the optimal concentration was 5 ng/ml(P<0.000 1). Compared with the 5 ng/ml TNF-α group, the expression of apoptosis gene in HT22 cells was inhibited by different concentrations of DOP, especially in the 20 μg/ml and 25 μg/ml groups(P<0.001), and the expression of related proteins in the 20 μg/ml and 25 μg/ml groups, the number and proportion of apoptosis in HT22 cells were significantly lower than those in the 5 ng/ml TNF-α group(P<0.001). Conclusion DOP can inhibit the apoptosis of HT22 cells induced by TNF-α, and the best inhibition effect is at the concentration of 20 μg/ml and 25 μg/ml.