Abstract: Objective To explore the effect of Janus kinase inhibitor AG490 on phosphorylation of STAT3 and ERK in the human breast cancer cell MDA-MB-231 and to study the cross-talking between JAK/STAT3 and ERK/MAPK signal transduction pathways and the roles of these two pathways on invasion and metastasis of human breast cancer cells. Methods MDA-MB-231 cellswere treated with Janus kinase inhibitor AG490.The expressions of P-STAT3,P-ERK were detected by Westernblot.The expressions of STAT3、ERK1、ERK2mRNA were measured by RT-PCR.Invasion and migration of MDA-MB-231 cell were investigated with transwell chamber.The secretion of MMP-2 and MMP-9 were tested by gelatin zymography. Results In MDA-MB-231 cells the expression level of P-STAT3、P-ERK and STAT3、ERK1、ERK2mRNA were decreased after treated with AG490,the secretion of MMP-2、MMP-9 were diminished，the invasion and migration of human breast cancer cells were also depressed. Conclusion Our study demonstrates that cross-talking occurs between transcription factor STAT3 and kinase ERK.STAT3 and ERK could affect each other's gene expression probably by phosphorylation interactions.The inhibiti on of JAK kinase could inhibit invasion and metastasis of human breast cancer cells through blocking these two pathways.