Silibinin, a flavonoid compound, has shown to be of chemopreventive potential against many cancers. However, its efficacy against gastric cancer has not been well elucidated. Here, we assessed the activity of Silibinin on apoptosis and cell-cycle arrest in human gastric cells culture system using SGC-7901 as the model. Silibinin treatment could inhibit the cell growth and cause a prominent G2 phase arrest and apoptosis in dose- and time-dependent manner. In mechanistic studies, Silibinin decreased the protein level of p34cdc2, which might be the possible molecular mechanism of Silibinin efficacy on the growth inhibition in SGC-7901 cells. In addition, Silibinin caused an increase in p53 and p21 protein level as well as mRNA levels. Interestingly, Silibinin-induced apoptosis in SGC-7901 cells was independent of caspases activation. These results indicated that Silibinin is a cell-cycle regulator and apoptosis inducer in human gastric carcinoma SGC-7901 cells and might be used as a candidate chemopreventive agent for gastric carcinoma prevention and intervention.