Objective: The purpose of this study was to explore the optimal cutoffs of the three parameters of Ki67 during NAC for predicting patient prognosis and investigate whether the optimal cutoffs of the Ki67 values were associated with relapse-free survival (RFS) or breast cancer-specific survival (BCSS). Methods: A total of 92 patients with locally advanced breast cancer (LABC), who had residual disease after NAC were retrospectively investigated. The optimal cutoff values of the Ki67 parameters were assessed by the online algorithm Cutoff Finder. Kaplan-Meier analysis, the log-rank test and Cox regression analysis were carried out to analyze survival. Results: The optimal cutoff values for the postsurgical Ki67 level and the decrease in the Ki67 level during NAC were defined as 25％ and 12.5％, respectively. According to the univariate survival analysis, a higher Ki67 level in residual disease was associated with poor RFS (P = 0.004) and BCSS (P = 0.014). In addition, a Ki67 expression decrease > 12.5％ during NAC was related to favorable RFS (P = 0.007), but was not related to BCSS (P = 0.452). Cox regression analysis showed that the Ki67 expression decrease (> 12.5％ vs. ≤ 12.5％) and histological grade (grade 3 vs. grade 1-2) were the independent factors associated with RFS (P =0.020 and P = 0.023, respectively), with HR values of 0.353 (95％ CI: 0.147-0.850) and 3.422 (95％ CI: 1.188-9.858), respectively. Conclusions: The Ki67 decrease was one of the independent factors associated with RFS in LABC patients with residual disease after receiving NAC.