C-X-C chemokine receptor type 4 (CXCR4)is a key regulator of cell motility in breast cancer (BrCa). Growing evidence has shown that CXCR4 signaling pathway is associated with the malignant progression of BrCa. The tyrosylproteinsulfotransferase 1 (TPST1)is an important enzyme for posttranslational tyrosines sulfation of CXCR4.This study is to investigate the role of TPST1 in CXCR4induced the invasion of BrCa cells. Using quantitative PCR, immunohistochemistry and western blot to test mRNA and protein expression of TPST1 and CXCR4 in BrCa tissues and cell lines. RNA interference, invasion assays and chemotaxis assays were used to evaluate the function of CXCR4 through TPST1 signal pathway in invasion of BrCa cells.In this study, the results showed that the high expression of CXCR4 protein was associated significantly with BrCa lymph nodes metastasis(χ² test, P=0.0016).There was a significant correlation between high CXCR4 expression with BrCa tumor infiltrating depth in metastatic lymph nodes (Pearson’s chisquare test, P=0.026).The expression of TPST1 and CXCR4 was positively correlated in BrCa primary tissues (Pearson’s correlation, r=0.364, P=0.009)and metastatic lymph nodes(Pearson’s correlation, r=0.382, P=0.006).TPST1 was strongly expressed in the highly malignant BrCa MDA-MB-231 cells compared to the less malignant BrCa MCF7 cells, with the same in total CXCR4 protein levels in these two cells. Expression of TPST1 small interfering RNA(TPST1siRNA)decreased the cell motility response to stromal cellderived factor 1 alpha (SDF1α)and reduced the invasiveness of MDA-MB-231 cells. In summary,TPST1 expression is necessary for CXCR4 function activation in the invasion of BrCa cells.TPST1 may be a potential antiCXCR4 combined target to the treatment of breast cancer malignant progression.