To explore the role of DR-nm23 in the regulation of colorectal cancer invasion and metastasis. Immunohistochemistry assay and in-situ nucleic acid hybridization were carried out to analyze the protein and mRNA expression of DR-nm23 in patient samples. The molecular cloning technique was applied to construct the recombinant lentiviral expression vector pGC-FU-DR-nm23-GFP. Lentiviral infection was used to introduce overexpression of exogenous DR-nm23 in SW620 colorectal cancer cells. Both in-vitro cell experiments and an in-vivo xenograft tumor model assay were carried out to determine the role of DR-nm23 in the regulation of colorectal cancer proliferation, invasion, and metastasis. Our data here showed that the expression level of DR-nm23 in colorectal cancer tissue was significantly lower than that in adenoma and normal tissue. The expression level of DR-nm23 was also found to be negatively correlated with lymph node metastasis and positively correlated with the degree of tumor differentiation. Besides, introduced overexpression of DR-nm23 in SW620 cells through lentiviral infection resulted in significant inhibition of its proliferation rate in vitro and growth rate in vivo. The cell migration ability in vitro and metastatic potential in vivo were also impaired at the same time. Our current study suggested that DR-nm23 may participate in the regulation of differentiation of colorectal cancer cells. Its downregulated expression is closely related to the invasion and metastasis of colorectal cancer. Thus, expression status of DR-nm23 may act as a potential prognostic factor in patients with colorectal cancer.