Purpose: This study examined the Cell differentiation and the anti-oxidative effect of Dioscoreae Rhizoma on HeLa cells. We are interested in whether Dioscoreae Rhizoma is capable of causing apoptosis processes on HeLa cell, and whether cotreatment of NCS with Dioscoreae Rhizoma reduces cell viability. Methods: We used aqueous extract to treat HeLa cell with different concentrations treated with a water or a MeOH extract of Dioscoreae Rhizoma (0, x10, x20, x40, x80). The MTT (3, (4, 5-dimethyl-thiazol) 2, 5-diphenyl-tetraxolium bromide) reduction assay was employed to quantify the differences in cell activity and viability. Cells were stained with DAPI and visualized by fluorescent Microscope. The caspase-3, Bcl-2, PARP, p53 expression level was monitored using western-blotting techniques. The patterns of the changes in expression were scanned and analyzed. Results: The survival rate of cells treated with Dioscoreae Rhizoma extracts increased by 20% at specific concentration. The other side Dioscoreae Rhizoma extracts induced apoptotic features including chromatin condensation and fragmentation. And Dioscoreae Rhizoma extracts increased the expression of caspase-3, p53 and the cleavage of PARP protein. However, co-treatment with Dioscoreae Rhizoma with NCS attenuated the activations of p53 and PARP protein that were mediated by NCS treatment alone. This is indicated Dioscoreae batatas extracts attenuated cytotoxicity induced by oxidative agents including NCS. Conclusion: Our results suggest Dioscoreae Rhizoma extracts induce cell differentiation or apoptosis connected with concentration. Further elucidation of concentration of Dioscoreae Rhizoma awaits many other biochemical investigative studies.