Objective To observe the impact of miR-539 on the invasion and migration of human thyroid carcinoma, and to investigate the interaction mechanism between miR-539 and caspase recruitment domain-containing membrane-associated guanylate kinase protein 1 (CARMA1). Methods  The ability of cells to migrate and invade was assayed using transwell inserts and MTT assay. The expressions of miR-539 and CARMA1 in thyroid cancer cells were detected by Western blot and RT-PCR. Results  miR-539 inhibited the invasion and migration of thyroid cancer cells. Luciferase reporter assay confirmed that miR-539 binding to the 3'-UTR region of CARMA1 inhibited the expression of CARMA1 in thyroid cancer cells. Further studies demonstrated that CARMA1 significantly promoted the migration and invasion of thyroid cancer cells. miR-539 changed as the expression of CARMA1 was regulated. Furthermore, the expression of miR-539 decreased while the expression of CARMA1 increased in thyroid cancer cell lines and thyroid cancer tissues compared with controls. Conclusions miR-539 can regulate migration and invasion in human thyroid cancer cells by targeting CARMA1.