Breast cancer is one of the most common malignant tumors among females. Recent studies demonstrated that microRNAs (miRNAs) played an important role in the regulation of tumor progression. In our present study, we firstly detected miR-340-5p expression in breast cancer cell lines and found lower expression of miR-340-5p in breast cancer cell lines (MCF-7, MDA-MB-231, BT-549, ZR-75-1) through qRT-PCR. Overexpressed miR-340-5p inhibited cell proliferation and drug resistance to docetaxel with enhanced cell apoptosis of breast cancer cells. Through bioinformatic prediction, we found that LGR5 was a potential target of miR-340-5p. LGR5 was highly expressed in breast cancer cells. Relative expression of LGR5 was negatively regulated by miR-340-5p. Knockdown of LGR5 also inhibited cell proliferation and drug resistance to docetaxel with enhanced cell apoptosis of breast cancer cells. Moreover, knockdown of LGR5 decreased the expression of β-catenin, c-myc, Survivin. The activation of Wnt/β-catenin pathway contracted the effects of LGR5 siRNA, indicating that LGR5 siRNA inhibited cell proliferation and drug resistance with induced apoptosis via suppressing Wnt/β-catenin signaling pathway in breast cancer. Taken together, our study demonstrated that overexpressed miR-340-5p inhibited cell proliferation and drug resistance with increased apoptosis of breast cancer cells through down-regulating LGR5 expression via Wnt/β-catenin pathway. The miR-340-5p/LGR5 axis may provide a new perspective for treatment for breast cancer.