Objective To investigate the value of CD66b⁺ tumor-associated neutrophils (TANs) and neutrophil to lymphocyte ratio (NLR) in evaluating the efficacy and prognosis of neoadjuvant chemotherapy (NACT) for breast cancer. Methods One hundred and sixty-seven patients of invasive breast cancer treated with NACT in the Department of Breast Surgery, the First People Hospital of Lianyungang from January 2015 to June 2020 were collected, and 40 cases of normal breast tissues were collected. Immunohistochemistry was used to detect the expression of CD66b in breast cancer tissues before NACT and normal breast tissues. Peripheral venous blood was taken from patients within 1 week before the first cycle of NACT, count neutrophils and lymphocytes were counted and their ratio (NLR) was calculated. The correlation between TANs and NLR and clinicopathologic features was analyzed by χ² test. The influencing factors of efficacy of NACT were analyzed by univariate χ² test and multivariate logistic analysis. Kaplan-Meier survival analysis and multivariate Cox analysis were used to determine the prognostic factors. The correlation between TANs and NLR was determined by Spearman test. Results The expression of CD66b in breast cancer tissues was significantly higher than that in normal breast tissues (P<0.05), and it was diffusely distributed throughout the tumor (cancer nest and stroma were infiltrated). High infiltration of parenchymal TANs before NACT was correlated with high clinical stage, lymph node metastasis, and recurrence and metastasis (P<0.05). High NLR before NACT was closely related to high cT stage and recurrence and metastasis (P<0.05). NLR of peripheral blood (P=0.007), cT stage (P=0.041), estrogen receptor (ER) status (P=0.009), and human epidermal growth factor 2 (HER2) expression (P=0.020) were independent predictors for pathologic complete response (pCR). TANs (P=0.023), high clinical stage (P=0.040), and pCR (P=0.027) before NACT were independent risk factors for disease-free survival (DFS) of patients with invasive breast cancer. There was no correlation between NLR and TANs (r=0.14, P=0.071). Conclusions Low infiltration of parenchymal TANs before NACT predicts a better prognosis for patients with breast cancer. Higher NLR in peripheral blood is associated with chemotherapy resistance.