Objective To design and synthesize a new series of efficient, low toxicity azole derivatives using antifungal drug ketoconazole as the lead compound and to explore their anti-breast cancer activity. Methods Based on the docking mode of ketoconazole with estrogen receptor, We designed and synthesized eleven derivatives, whose 2, 4-dichlorophenyl and triazole ring were retained and the side chains were modified. Then the in vitro anticancer activities against breast cancer cells MDA-MB-231 and MCF-7 were determined by MTT using tamoxifene as the positive control drug. Results and Conclusion The synthesized compounds have been reported for the first time and they have been confirmed by ¹HNMR and ¹³CNMR. The synthesized azole derivatives have greater inhibitory effects than tamoxifene against breast cancer MDA-MB-231 cells.