Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor that plays critical roles in the pathogenesis of several human diseases including tumor metastasis and Alzheimer's disease. However, mechanisms that regulate LRP1 expression under physiological and pathophysiological conditions are not unclear. In human cell lines, we found that miR-205 down-regulates the expression of LRP1 by targeting sequences in the 3'UTR of LRP1 mRNA. This effect was abolished by deleting the miR-205 seed site in the 3'UTR of LRP1. The ectopic expression of miR-205 also significantly mitigated migration of both U87 and SK-LU-1 cells. These results, for the first time, demonstrate that expression of human LRP1 is regulated in part by a specific miRNA, leading to decreased tumor cell migration.