Previous studies have demonstrated that miR-486-5p functions as a tumor suppressor or oncogene in various types of cancer. In the present study, we showed that miR-486-5p was significantly down-regulated in papillary thyroid carcinoma (PTC) tissues and cell lines, whereas miR-486-5p down-regulation inhibited PTC cell proliferation and increased apoptosis. Conversely, under-expression of miR-486-5p enhanced PTC cell proliferation and decreased apoptosis. Fibrillin-1 (FBN1) was shown to be a direct target of miR-486-5p and inversely regulated by miR-486-5p. FBN1 silencing led to decreased PTC cell proliferation and enhanced apoptosis in vitro, similar to that mediated by miR-486-5p. Furthermore, miR-486-5p over-expression or FBN1 knock-down inhibited, while up-regulation of FBN1 boosted xenograft tumor formation in vivo. Our data suggest that miR-486-5p induces PTC cell growth inhibition and apoptosis by targeting and suppressing FBN1. Thus, miR-486-5p/FBN1 might provide a promising therapeutic target for PTC treatment.