Objective: To discuss the combination of shear-wave (SWE) and Ki-67 index for predicting the pathological response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. Methods: Sixty eligible patients with breast cancer were consecutively included. The mean and maximum stiffness of breast cancer were evaluated by SWE before biopsy, one NAC cycle after the first and the second cycle of NAC. The relative change of SWE readings after first and second cycle was also considered as the variables [ΔE(t1), ΔE(t2)]. Pathologic response as the golden standard was classified according to Miller-Panye grade protocol. Based on the linear regression model PredRCB = 4.449 + 3.617 × ΔEmean(t2) − 0.026 × Ki-67, The new index PredRCB was obtained for each tumor. The predictive diagnostic performances of SWE parameters, Ki-67 and predRCB were compared by area under receiver operation characteristic and its 95% confidence interval. Results: The ΔEmean(t2) and Ki-67 showed significantly better diagnostic performance than other parameters in the predicting favorable pathological response and resistance to NAC, respectively. However, Pearson correlation analysis showed that the correlation between ΔEmean(t2) and Ki-67 index was significantly weak (r=−0.38, P<0.01). Furthermore, Z test indicated that the predRCB showed better overall diagnostic performances than SWE parameters and Ki-67 alone (P<0.05). Conclusion: The combination of SWE and Ki-67 index can improve overall predictive diagnostic efficiency of NAC pathological responses evaluated by Miller-Panye grade classification.