Papillary thyroid cancer is one of the most common tumours subtype in thyroid cancers. Substantial amount of data have indicated that miR-16 is an important regulator of various tumours; however, the molecular functions of miR-16 in papillary thyroid cancer remained largely elusive. In order to investigate the regulation of miR-16, human papillary thyroid carcinoma cells are transfected with miR-16 mimics or inhibitors. Targeting miR-16 and using dual-luciferase reporter assay, qRT-PCR and Western blot, the mRNA and protein expression were detected, respectively. Cellular apoptosis were examined by flow cytometry and Western blots was applied to assess the cleaved caspase-3, -8, -9, and cleaved poly-ADP-ribose polymerase. Protein expression of extracellular-regulated kinase were detected. Finally, data analysed statistically to determine significantly differences among groups. Results showed that breakpoint cluster 2 was a direct target of miR-16, and the expression was negatively correlated. Moreover, miR-16 promoted apoptosis suppressing breakpoint cluster 2 through phosphorylation of extracellular-regulated kinase. The study validates miR-16 as a tumour suppressor gene in papillary thyroid cancer cells, and revealed a novel mechanism of miR-16-mediated apoptosis through extracellular-regulated kinase pathway.