Objective To explore the influencing factors of pathological complete response（pCR）by neoadjuvant chemotherapy（NAC）combined with targeted therapy for Her⁃2 positive breast cancer. Methods The clinical and pathological data of 185 patients with HER⁃2 positive breast cancer who were initially diagnosed and received NAC combined with targeted therapy were retrospectively analyzed. Univariate and multivariate analysis were used to find the factors associated with pCR. Results The overall pCR rate was 53.5%. Estrogen and proges⁃ terone receptor status，HER ⁃2 positive mode of diagnosis，and targeted therapy regimen were independent factors associated with pCR rate（P < 0.05）. Patients with hormone receptors negative were more likely to achieve pCR than positive（OR = 4.829，95%CI：2.399 ~ 9.721，P < 0.001），patients with HER⁃2 2+ and FISH positive were less likely to achieve pCR than HER⁃2 3+（OR = 0.430，95%CI：0.191 ~ 0.971，P = 0.042），and patients with dual ⁃target therapy were more likely to achieve pCR than single ⁃target therapy（OR = 2.203，95%CI：1.147 ~ 4.232，P = 0.018）. Conclusions Her⁃2 positive breast cancer patients with hormone receptor negative，Her⁃2 3+ or double target therapy are more likely to obtain pCR in NAC combined with targeted therapy.