Abstract: Objective To investigate the effect of gypenosides (Gyp) on proliferation and apoptosis of oral squamous cell carcinoma cell line SCC9 and to explore its underlying mechanism. Methods SCC9 cells were cultured with different concentrations of Gyp (70, 85 and 100 μg/ml), the untreated with Gyp as a control group (Ctrl group). Cell proliferation was detected by MTT assay. Apoptosis was detected by flow cytometry. The mRNA and protein expression of Notch1 and Jagged1 were detected by real-time PCR and Western blot. Results The proliferative rates of SCC were 62.15±8.13, 50.08±7.14 and 24.83±5.63 at Gyp concentrations of 70, 85 and 100 μg/ml, respectively, which were significantly lower than those in Ctrl group (P<0.05); the apoptotic rates were 23.54±2.17, 37.01 3.62 and 60.03±7.85, respectively, which were significantly higher than that of the Ctrl group (P<0.05); Notch1 mRNA expression was 2.24±0.17, 2.46±0.23, 2.97±0.31; the protein expression was 0.98±0.08, 1.26±0.09 and 1.71±0.13, respectively, which were significantly higher than that of the Ctrl group (P<0.05); Jagged1 mRNA expression were 0.94±0.11, 0.51±0.09, 0.26±0.06; the protein expressions were 1.43±0.15, 0.73±0.08 and 0.24±0.06, respectively, which were significantly lower than those in the Ctrl group (P<0.05); the fluorescence intensity of SCC9 cells were 65.69±11.32, 113.12±15.94 and 163.32±19.48 respectively, which were significantly higher than that of the Ctrl group (P<0.05). Conclusion Gyp can inhibit the proliferation and induces apoptosis of OSCC cell line SCC9 in a dose-dependent manner. Notch signaling pathway activation plays an important role in this process.