Expression of trans-activation-responsive-RNA-binding protein 2 (TARBP2) varied from normal cell lines to various cancer cell lines. The discussion of TARBP2 serve as tumor suppressor or tumor promotor goes on. However, its expression in breast cancer remains unknown. The aim of present study was to assess the expression of cytoplasm TARBP2 as potential prognostic marker in breast cancer. We further investigated cytoplasm TARBP2 could be a novel target in treatment for late-stage breast cancer and triple-negative breast cancer (TNBC). A total of patients with breast cancer were involved in our cohort. Immunohistochemical staining for TARBP2 on tissue microarray and western blot were used. Immunohistochemistry showed that cytoplasm TARBP2 was frequently up-regulated in breast carcinoma. This finding was in line with the result of western blot analysis. Further investigation showed that cytoplasm TARBP2 expression in non-TNBC was higher than that of their adjacent normal breast tissues (NBT), and TNBC was the highest of the three groups. The positive expression of cytoplasm TARBP2 in stage III breast cancer, stage I-II breast cancer, and NBT decreased gradually. In addition, univariate and multivariate survival analysis revealed cytoplasm TARBP2 was an independent prognostic factor for breast cancer. Breast cancer patients with cytoplasm TARBP2 expression had poorer disease-free survival and overall survival, and similar results were obtained in TNBC group and stage III breast cancer group. Our results provide convincing evidence for the first time that the expression of cytoplasm TARBP2 is up-regulated in breast cancer. Breast cancer patients with TARBP2 cytoplasm expression have unfavorable prognosis. Patients of TNBC and late-stage breast cancer with higher cytoplasm TARBP2 expression have an unfavorable prognosis.