Purpose of Investigation: To investigate the mechanism of apoptosis of AN3CN cells, an endometrial cancer (EC) cell line, induced by human umbilical cord mesenchymal stem cells (hUCMSCs). Materials and Methods: UC-MSCs and AN3CN cells were co-cultured and CCK-8 cell proliferation assay was used to assess cell proliferation. Results: By co-culture with hUCMSCs, the proliferation of AN3CN cells was significantly inhibited (p < 0.001) and the cell cycle of AN3CN cells was arrested in the G2 phase. Furthermore, this study indicated that changes in the PI3K/Erk/JNK/Bcl-2/DR5 signal pathway-related genes promoted apoptosis of AN3CN cells. Conclusion: This finding not only helps us understand the molecular mechanism of hUCMSCs inhibiting tumor growth and promoting apoptosis, but also provides us a strong rationale to further investigate hUCMSCs as a potential treatment of EC.