Cancer is a disease of cell cycle, characterized by uncontrolled cell division. The tumor suppressor gene p53 plays a major role in cell cycle control, blocking the cell progression at G 1 /S phases. In triple negative breast cancer (TNBC), the lack/mutation of p53 is a common genetic irregularity that promotes survival signals leading to tumorigenesis. Due to its unique molecular profile, aggressive behavior, and metastasis, no targeted therapies exist for TNBC. This motivates our exploration of the influence of Electro-Curcumin-Therapy on the viability, cell cycle and p53 expression profile of TNBC cells. MDA-MB-231, human TNBC cells were treated with curcumin and eight 200 V cm −1 electric pulses (EPs) of either 100 μs or 5 ms duration. The synergy of 5 ms EPs and curcumin reduced viability to as low as 6% at 48 h after treatment. Combining the 100 μs EPs with curcumin arrested 80% cells in the G 0 /G 1 phase. Applying 5 ms EPs with curcumin caused cells to shift from the G 2 phase (9% reduction) to the S phase population (21% increase) compared to control. Combining 100 μs EPs with curcumin significantly downregulated the p53 level, while the p53 level significantly increased for 5 ms EPs with and without curcumin. These results indicate the potent effect of combining EPs and curcumin to effectively cause cell death in TNBC cells with different mechanistic behaviors, while having a much-reduced impact on cell death in normal mammary cells.