Objective The relationship between the expression of kinesin family member 15 (KIF15) and clinicopathological features in breast cancer (BC) remains controversial. In this study, we aimed to explore the influence of KIF15 expression on the efficacy of neoadjuvant chemotherapy (NAC) and evaluate its clinical value in predicting prognosis for BC patients. Methods Immunohistochemistry was used to detect KIF15 expression in 93 BC patients undergoing NAC to analyze the relationship between KIF15 expression and clinical efficacy and analytical parameters. Results Of the 93 BC patients enrolled, 24.73％ who underwent NAC had higher KIF15 expression levels, showing positive correlations with ER, HER-2, Ki67, and lymph node metastasis (P < 0.05). The clinical benefit of NAC was 70.97％, and the major histological response (MHR) rate was 61.29％. The effective therapeutic rate in patients with high KIF15 expression was 95.65％, while the MHR rate was 65.22％. Various molecular BC subtypes with varied clinical and pathological responses exhibited correlation to a large extent. Of all the BC patients studied, 84％ of the triple-negative breast cancer (TNBC) patients were evaluated as clinically effective, and 52％ of the TNBC patients were evaluated as pathologically effective, and these values were significantly higher than those of the other molecular types (P < 0.05). The expression of KIF15 in 25 TNBC patients showed positive correlations with lymph node metastasis. Conclusion Overexpression of KIF15 was shown to increase BC sensitivity to chemotherapy and demonstrated better outcomes.