The microRNA-146b-5p (miR-146b-5p) is known to be involved in the development of papillary thyroid cancer (PTC); however, the underlying mechanism is unclear. Here we have investigated the biological functions and underlying molecular mechanisms of miR-146b-5p in PTC. The expression of miR-146b-5p was assessed in 92 pairs of PTC and adjacent normal tissues and showed correlation with the clinicopathological status such as the tumour size. Effects of miR-146b-5p and its direct target, coiled-coil domain containing 6 (CCDC6), on cell proliferation, migration, invasion, and cell cycle were evaluated through gain- and loss-of-function studies in vitro and in vivo. The expression of CCDC6 was further examined in 187 PTC cases and was found to be correlated with the clinicopathological status. Overexpression of miR-146b-5p was observed in PTC tissues that correlated with advanced PTC. miR-146b-5p promoted cell proliferation, migration, invasion, and cell cycle progression in vitro, whereas CCDC6 reversed this effect. miR-146b-5p promoted PTC growth in a subcutaneous mouse model in vivo, whereas overexpression of CCDC6 exerted the opposite effect. In conclusion, miR-146b-5p expression correlated with advanced PTC and promoted PTC development by targeting CCDC6 in vitro and in vivo; it could, therefore, serve as a promising target for PTC treatment.