Objective:To observe the biological changes of human gastric cancer cell line SGC－7901, which was stably transfected with siRNA targeting osteopontin (OPN) and to study the molecular mechanism related to the biological changes. Methods:SGC－7901 cells were transfected with OPNsiRNA－pcDNATM6.2 and pcDNATM6.2 by lipofectamine 2000. Transfectants were selected and confirmed by Western blot and RT－PCR technique. The proliferation activity was detected by MTT assay and cell apoptosis was tested by flow cytometry. The migration of transfected cells was assayed by using transwell migration chambers. The expressions of OPN,CXCR4,MMP2 on mRNA and protein level were determined by RT－PCR and Western blot. Result:SGC－7901 cells were stably transfected with OPNsiRNA－pcDNATM6.2. MTT showed that the growth of OPNsiRNA transfected cells was slower than that of empty vecter transfected cells. OPNsiRNA gene transfection can increase the apoptosis. The migration of cells transfected with OPNsiRNA was suppressed compared with the cells transfected with empty vector,and the expressions of CXCR4 and MMP2 in SGC－7901 cells were significantly suppressed after OPN silenced by RNA interference. Conclusion:After OPN siRNA treatment,the cell proliferation and motility are suppressed,and apoptosis is enhanced;CXCR4 and MMP2 are OPN targeting genes. OPN may regulate the growth and metastasis of tumor cell via SDF－1/CXCR4 axis and MMP2 involved signaling pathway.