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Objective To explore the effects of tamoxifen (TAM) on the invasion, activity and expression of matrix met-alloproteinase-9 (MMP-9) in breast cancer MCF-7 cells, meanwhile to discuss the role of inhibiting G-protein-coupled receptor 30 (GPR30) in these effects. Methods MCF-7 cells in the logarithmic phase were pre-cultured for 24 h in phenol red (PR)-free medium without serum to remove endogenous estrogen before the indicated treatments. MCF-7 cells were seeded in the six-well plates and incubated over night to let them adhere on the plate. The control group was continued to cultivate in PR-free medium without serum for 24 h. The TAM group was treated with 1 μmol/L TAM in PR-free medium without serum for 24 h. And the TAM+G15 group was pretreated with G15 (1 μmol/L) for 30 min before treatment with TAM (1 μmol/L) for 24 h in PR-free medium without serum. After treatment, cell invasion was detected by Transwell assay. The activity of MMP-9 in culture medium was tested by Gelatin zymography assay. The MMP-9 protein expression was analyzed by Western blotting. The mRNA expression of MMP-9 was tested by real-time RT-PCR. Results Compared with control group, the cell invasion was increased, the protein and mRNA expression level of MMP-9 was up-regulated, and the activity of MMP-9 in MCF-7 cells was increased in the TAM group (all P <0.05). Furthermore, compared with the TAM group, the above indexes of the TAM+G15 group were all decreased (all P <0.05). Conclusions TAM promotes the cell invasion ability and up-regulates the activity and expression of MMP-9. Meanwhile, the effects may be suppressed by G15 pretreatment. [ABSTRACT FROM AUTHOR]