Background and Aims Trastuzumab mainly acts on the HER-2-HER-2 homodimer, but exerts little effect on the signaling pathway of ligand-induced HER-2 heterodimers. Pyrotinib can completely block the downstream pathway of the homo- and heterodimers of the HER family. Therefore, based on the different action mechanisms of the two drugs, this study was conducted to investigate the short-term efficacy and safety of the neoadjuvant chemotherapy regimen of pyrotinib combined with TCbH regimen (docetaxel, carboplatin and trastuzumab) in the treatment of young patients with locally advanced HER-2 positive breast cancer at first diagnosis.Methods From October 2018 to January 2020, 32 young patients with first diagnosis of locally advanced HER-2 positive breast cancer admitted in the Affiliated Suqian Hospital of Xuzhou Medical University were selected as study subjects. The patients were randomly divided into two groups, of whom, 16 patients received pyrotinib plus TCbH regimen (observation group), and the other 16 patients received TCbH regimen alone (control group). The treatment efficacy and adverse reactions of the two groups were compared.Results In observation group, 2 patients achieved clinical complete response (cCR) after 4 cycles of treatment and asked for surgical treatment, and the postoperative pathology demonstrated pathologic complete response (pCR); 5 patients achieved cCR after 6 cycles of treatment, then underwent surgical treatment, and the postoperative pathology revealed pCR; the remaining 9 patients showed obvious tumor regression after 6 cycles of treatment, but did not reach cCR, and the pathology showed non-pCR after surgical treatment. The total pCR rate was 43.8% (7/16). In control group, 4 patients achieved cCR after 6 cycles of treatment and received surgical treatment, postoperative pathology showed pCR, the pathological findings of the remaining 12 patients were non-pCR after 6 cycles of treatment, the total pCR rate was 25.0% (4/16). There was a statistical difference in total pCR rates between the two groups (χ²=4.800, P=0.028). The incidence rates of diarrhea and hand foot syndrome in observation group were higher than those in control group (both P<0.05), which were tolerable in all patients after symptomatic treatment; there were no significant differences in incidence rates of other adverse reactions caused by chemotherapy between the two groups (all P>0.05); no cardiotoxicity events occurred in both groups.Conclusions The neoadjuvant therapy of pyrotinib combined with TCbH regimen can significantly improve the pCR rate of locally advanced HER-2 positive breast cancer, with satisfactory curative effect and tolerable adverse reactions. It may be used as another preferred regimen besides TcbHP (docetaxel, carboplatin, trastuzumab and pertuzumab) regimen.