Our results showed that overexpressed miR-1284 in both MG-63 and U2OS cells significantly inhibited the HMGB1 mRNA and protein expression and further resulted in a reduced cell proliferation and migration of osteosarcoma cells, which might be caused by the increase in E-cadherin protein level and decrease in N-cadherin, Vimentin, and Snail protein levels. Here, HMGB1 is linked to osteosarcoma.