Introduction: The crucial and vital player in tumor recurrence is the tumor - initiating cells (TICs). OCT4 is a widely appreciated non -cell surface for TICs, dedicating detrimental properties to these cells, including self-renewal, epithelial -mesenchymal capacity, and drug resistance. OCT4 and its partners Sox2 and Nanog are up -regulated in stem cells; on the other hand, normal stem cells are more resistant to various herbal remedies like curcumin. Based on these facts, the main objective of the present study was to investigate the alteration of the mentioned genes expression after curcumin treatment in breast cancer cell, human bone marrow mesenchymal stem cells (hBM -MSCs), and non -tumor fibroblast cells (HSFPI3). Materials and Methods: MTT assay and AnnexinV/PI were performed to calculate the effective concentration of curcumin. To assess the expression level of OCT4 and Nanog, real -time PCR was performed to quantify the alteration of the mRNA expression of the mentioned genes after treatment in MDA -MB231, hBM -MSCs, and HSFPI3. Results: Curcumin could not induce significant apoptosis in hBM -MSCs and HSFPI3 even after 24 and 36 hours after treatment in a toxic concentration for cancer cells. After 36 -hour treatment with DNC, the mRNA expression of Oct4 -B1 in both normal cells enhanced significantly compared to untreated samples. Furthermore, in HSFPI3 cells, the Nanog mRNA expression increased after this treatment. The expression of both genes decreased in the MDA - MB231 after treatment with DNC. Conclusion: Non -tumor cells are more resistant to the curcumin treatment compared to cancer cells. The reason is at least partially due to the different expression pattern results in these cells after treatment with this reagent. Pluripotent markers, including Oct4 -B1 and Nanog are proposed to play a vital role in these non -tumor cells resistant to curcumin.