To investigate the effect of DPC4 gene on invasion and metastasis of colorectal carcinoma cells, the expression of DPC4 was detected in sixty-three samples of colorectal tumors and seven cases of colorectal mucosa. The biological behavior of tumors expressing DPC4 was evaluated (including tumor staging, differentiation degree and metastasis). pcDNA3.1-DPC4 plasmid was constructed and transferred into HCT116 cells not expressing DPC4. The cell models (DPC4(+)-HCT116) steadily expressing DPC4 were obtained. Compared with HCT116 and pcDNA3.1-HCT116 cells, the doubling time of DPC4(+)-HCT116 cells was lengthened obviously (P<0.01), the apoptosis rate of DPC4(+)-HCT116 cells was significantly increased (PP<0.01), the cloning efficiency, cell adherency, migration and invasion ability of DPC4+-HCT116 cells were dropped obviously (P<0.01). The number of cancer nodules was decreased significantly in abdominal cavity and liver of the nude mice inoculated with DPC4(+)-HCT116 cells. The activity of MMP-9 and MMP-2 was detected by gelatin zymography. In comparison with HCT116 and pcDNA3.1-HCT116 cells, the activity of MMP-9 was decreased in DPC4(+)-HCT116 cells. Therefore, the down-regulation of DPC4 expression may be associated with the carcinogenesis of colorectal carcinoma. DPC4 may inhibit the proliferation of colon cancer cell by restraining growth and inducing apoptosis, and the invasion and metastasis of colorectal carcinoma cells. MMP-9 may be one of the downstream target genes regulated by DPC4.