Objective: to analyze the effect of CD68 protein of tumor-associated macrophage and the clinicopathological features of breast cancer on the efficacy and prognosis of neoadjuvant chemotherapy (NCT). Methods: In January 2013 to January 2017, 172 cases of patients with Locally advanced breast cancer in the Affiliated Drum Tower Hospital of Medical College of Nanjing University were selected as the research objects. ER, HGR2, Ki-67, and the expression of CD68 were detected by immunohistochemical. All patients were given surgery within 1 month after NCT. Clinical pathology analysis parameters and pathological complete response rate (pathologic complete response, pCR) relationship was analysed. Results: CD68 expression was negatively correlated with ER (r=−0.129, P=0.018), CD68 expression was positively correlated with HER2 (r=0.211, P=0.011), Ki-67 (r=0.195, P=0.013) and tumor diameter (r=0.315, P=0.007), while there was no significant correlation between CD68 and patient age, menopausal status and lymph node metastasis (P>0.05). The pCR rate of ER negative group (25.95%) was significantly higher than that of the positive group (7.81%) (P<0.05). The pCR rate (32.39%) of the Ki-67 group with high expression was significantly higher than that of the group with low expression (9.90%) (P<0.05). The pCR rate (24.11%) of the group with high CD68 expression was significantly higher than that of the group with low expression (10.00%) (P<0.05). After chemotherapy, the expression of CD68 decreased, the pCR ratewas 24.43% (32/131) in the decreasing group, and the pCR rate was 2.44% (1/41) in the non-decreasing group (no change or rise) , suggesting that the change of CD68 after chemotherapy was correlated with the efficacy of chemotherapy (P<0.05). The molecular subtypes were significantly correlated with menopausal status, tumor diameter before chemotherapy, efficacy and CD68 expression before chemotherapy (P<0.05), but not with age or lymph node metastasis (P>0.05). Before chemotherapy, both OS and DFS in the group with low CD68 expression were superior to the group with low and high CD68 expression (P<0.05). After chemotherapy, both OS and DFS in the CD68 decreased group were longer than those in the decreasing group (P<0.05). COX multivariate regression analysis showed that the changes of ki-67, CD68 before chemotherapy and CD68 after chemotherapy were independent risk factors affecting DFS. Conclusion: High expression of CD68 was more sensitive to chemotherapy, but the prognosis was poor. Changes of ki-67, CD68 and CD68 after chemotherapy are independent risk factors affecting DFS, and ki-67, ER, HGR2, CD68 and molecular subtypes can be used as predictors of the efficacy of NCT.