Osteosarcoma (OS), a common and primary malignant bone tumor, is characterized by highly aggressive potency. Baicalein, a bioactive flavone isolated from Scutellaria baicalensis Georgi, has been shown to inhibit the progression of numerous tumors, including OS. However, the mechanisms by which baicalein protects against OS are still largely unknown. The results of the present study showed that administration of baicalein significantly inhibited the proliferation, migration and invasion and promoted apoptosis in MG‑63 and Saos‑2 cells. Ezrin was identified as a target gene of microRNA (miR)‑183. MG‑63 and Saos‑2 cells treated with baicalein exhibited increased miR‑183 levels and decreased Ezrin expression. Importantly, miR‑183 inhibition and Ezrin overexpression abolished the effects of baicalein on MG‑63 and Saos‑2 cell proliferation, migration, invasion and apoptosis. Taken together, these findings suggest that baicalein inhibits the proliferation, migration and invasion and induces apoptosis in OS cells by activating the miR‑183/Ezrin pathway, revealing a novel mechanism underlying anti‑OS effects of baicalein.