Objectives Despite remarkable development of new therapeutic strategies to improve survival rates and treatment of patients with cancer, there are still many limitations in management of patients with distant metastasis breast cancer. Therefore, the aim of this study was to investigate a novel method to enhance therapeutic efficacy of Apatinib (as a chemotherapeutic agent) by co‐administration of Curcumin (as a bioactive herbal compound) in breast cancer treatment. Methods Effects of Apatinib, Curcumin, and their combinations (Apa‐Cur) was evaluated on viability and proliferation of breast cell line (MCF7) by MTT assay. Moreover, effects of Apatinib, Curcumin, and Apa‐Cur was investigated on apoptosis rate in the cancer cells. Expression levels of apoptosis-related genes (BAX, SMAC, BCL2, and SURVIVIN) in treated cancer cells and untreated controls were evaluated using the Real-Time PCR method. Results The obtained results showed that all treatments of Apatinib, Curcumin, and Apa‐Cur significantly decreased viability and proliferation of the breast cancer cells in a concentration‐ and time‐dependent manner. However, anti-proliferation activity of Apa‐Cur combination was significantly higher than Apatinib and Curcumin treatment alone. In addition, Apatinib, Curcumin, and Apa‐Cur increased apoptosis percentage in the treated cancer cells through regulation of apoptosis-related genes expression. Conclusions In general, Apa‐Cur combination therapy exerts more profound anti-proliferation effects on breast cancer cell than Apatinib or Curcumin monotherapy. However, further studies are required to identify other possible signaling pathways and mechanisms involved in the anticancer effects of Apatinib, Curcumin, and Apa‐Cur.