Background: We have previously found that S100 calcium-binding protein A7 (S100A7) is strongly associated with chemoresistance in breast cancer (BC). In this study, we investigated whether S100A7 can be used to predict the efficacy of neoadjuvant chemotherapy (NAC) and assessed its relationship with clinicopathological characteristics in BC. Methods: We retrospectively analyzed the clinicopathological data of patients with BC who underwent NAC at the Fourth Hospital of Hebei Medical University between January 2021 and December 2021. The t-test, Wilcoxon test, and chi-square test were used to compare clinicopathological characteristics between the NAC-sensitive and NAC-insensitive groups and assess the relationship between S100A7 expression and clinicopathological characteristics. Binomial logistic regression analysis was used to identify the predictors of NAC efficacy. A prediction model was constructed and visualized using a nomogram for clinical prediction of NAC efficacy. Results: A total of 76 patients with BC who underwent NAC were included in this study; of these patients, 49 were sensitive to NAC, whereas 27 were insensitive to NAC. Statistically significant differences were observed in age, menstrual status, histological grade, T stage, Ki67, and S100A7 expression between the NAC-sensitive and NAC-insensitive groups. Regression analysis showed that age, histological grade, Ki67, subtype, menstrual status, TILs and S100A7 expression were predictors of NAC efficacy. However, only histological grade III (OR, 25.613; 95% CI, 1.254-523.077; P = 0.035), Ki67 (OR, 9.781; 95% CI, 2.022-47.317; P = 0.005), TILs (OR, 1.227; 95% CI, 1.064-1.415; P = 0.005), and S100A7 expression (OR, 0.042; 95% CI, 0.010-0.174; P<0.001) were independent predictors. Therefore, we constructed a model incorporating these four characteristics and visualised the model in a nomogram to predict NAC efficacy in clinical settings, with a model prediction accuracy of 0.927. Conclusion: S100A7 may serve as a predictor of NAC efficacy in patients with BC.