Abstract: Objective: To investigate the LncRNA-ATB in promoting invasion and metastasis of breast cancer cells and the trastuzumab resistance in clinical and molecular mechanisms. Methods: From September 2012 to September 2013, 15 cases of surgical resection of trastuzumab resistance of breast cancer patients in our hospital were collected, and RT-PCR detected the level of lncRNA-ATB mRNA in paired tissue; Follow-up after the surgery for a period of 36 months; Kaplan-Meier method was used to drawn the curve of patients with lncRNA-ATB expression and progression (PFS), overall survival (OS); Using normal mammary gland cells MCF-10A and breast cancer cell lines MCF-7, MDA-MB-435S, T47D and ZR-75-30, RT-PCR detected the level of LncRNA-ATB mRNA; CCK8 determined the change of trastuzumab resistance after lncRNA-ATB silencing. Flow cytometry was measured the apoptosis rate induced by trastuzumab; Transwell and wound healing assays determined the effect of LncRNA-ATB on invasion and metastasis of breast cancer cells; Western blot detected the level of MDR1 and epithelial-mesenchymal transition index (E-cadherin and Vimentin). Results: The mRNA level of lncRNA-ATB in patients with breast cancer in cancer tissues was significantly higher than that in adjacent tissues (P<0.05). The high expression of lncRNA-ATB indicate with short survival time of patients (P<0.05); lncRNA-ATB knockout significantly reduced the cell sensitivity to trastuzumab, the IC50 decreased from 120.54 M to 59.65 M ( P<0.05), and the level of apoptosis induced by trastuzumab was significantly increased (P<0.05); In addition, the abilities of invasion and migration cells were decreased significantly; Western blot showed the expression of resistance protein MDR1 was decreased significantly, and lncRNA-ATB silencing was significantly reversed EMT processing. Conclusion: lncRNA-ATB play important role in the development of trastuzumab resistance and related to the abilities of migration and invasion of breast cancer. LncRNA-ATB may be a potential target for treatment and a potential target for treatment of breast cancer.