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Objective To investigate the expression of kinesin KIF18B in breast cancer cells and its impact on the cell proliferation, apoptosis, and prognosis of estrogen receptor-positive(ER+) breast cancer. Methods The expression of KIF18B mRNA were detected using real-time fluorescent quantitative PCR in ER+ breast cancer cell lines and clinical specimens of ER+ breast cancer tissue. Two ER+ breast cancer cell lines (YCCB1 and T47D) were transfected with a small interfering RNA targeting KIF18B, and the changes in the proliferative activity and apoptosis of the cells following KIF18B silencing were investigated using a CCK-8 kit and flow cytometry, respectively. Kaplan-Meier analysis was performed to assess the value of KIF18B in evaluating the prognosis of patients with ER+ breast cancer. Results KIF18B was highly expressed in ER+ breast cancer cell lines and clinical specimens (P < 0.05). KIF18B silencing significantly suppressed the proliferation and enhanced apoptosis of the 2 ER+ breast cancer cell lines (P < 0.05). Analysis of Kaplan-Meier showed that ER+ breast cancer patients having a high expression of KIF18B mRNA had poorer overall survival and recurrence-free survival than those with a low KIF18B expression (P < 0.05); in the patients receiving tamoxifen therapy, a high expression level of KIF18B mRNA was associated with a poorer distant metastasis-free survival (DMFS) and recurrence-free survival (P < 0.05). Conclusion ER+ breast cancer expresses high level of kinesin KIF18B, which promotes the proliferation and enhances apoptosis resistance of the tumor cells. A high expression of kinesin KIF18B predicts a poor prognosis of patients with ER+ breast cancer.