Hormone receptor-positive (HR+) breast cancer accounts for approximately 70% of all breast cancers, with tamoxifen being a key therapeutic option for estrogen receptor-positive (ER+) cases. However, triple-negative breast cancers (TNBC), lacking ER expression, remain unresponsive to this treatment. Nanocurcumin, a bioactive compound with epigenetic-modulating properties, has shown potential in reactivating ESR1 expression by inhibiting DNA methyltransferases. This study investigates the effect of nanocurcumin on ESR1, CyclinD1, and KRAS gene expression in MDA-MB231 cells, a tamoxifen-resistant TNBC cell line. The IC50 of nanocurcumin was determined through MTT assay. Gene expression levels were analyzed using qRT-PCR, and apoptosis and cell cycle distribution were assessed via flow cytometry and Annexin V assays. Our results show a significant increase in ESR1 expression and a concurrent decrease in CyclinD1 and KRAS expression in nanocurcumin-treated cells compared to controls. Apoptosis rates were higher, and cell cycle analysis revealed G1 phase arrest. These findings suggest that nanocurcumin may reverse epigenetic silencing of ESR1, enhance tamoxifen sensitivity, and suppress downstream oncogenic pathways by inhibiting KRAS and CyclinD1.