Objective：To explore the effect of dominant negative epidermal growth factor receptor（DNEGFR） on the invasion and metastasis of human gastric cancer cells and to elucidate its molecular mechanism. Methods：The pEGFPN1-DNEGFR was construct－ed and human gastric cancer cells were transfected stably. The invasion and metastasis in vitro were tested by Transwell invasion cham－ber assay. Matrix metalloproteinase-2（MMP-2） and Matrix metalloproteinase-9（MMP-9） mRNA levels of cells were detected by re－versed transcription-polymerase chain reaction（RT-PCR）. MMP-2 and MMP-9 protein levels of culture were detected by enzyme-linked immunosorbent assay（ELISA）. Results：pEGFPN1-DNEGFR was constructed successfully，human gastric cancer cells was transfected stably. MMP-2 and MMP-9 mRNA levels of cells were down-regulated；MMP-2 and MMP-9 protein levels of culture were down-regulated as well. Conclusions：DNEGFR represses the invasion and metastasis of human gastric cancer cells by inhibiting them from secreting MMP-2 and MMP-9，which lays a solid foundation for further research of DNEGFR in gastric cancer biotherapy.