The Vermillion River is a tributary of the Missouri River, 96 miles (154 km) long, in eastern South Dakota in the United States. The origin of the river name is , Lakota for "place where vermilion is obtained".
It is formed by the confluence of the East Fork Vermillion River and West Fork Vermillion River. The East Fork, approximately long, and south of Vermillion. Its tributaries include White Stone Creek and Baptist Creek. The Vermillion River drains about of the southwestern edge of the Coteau des Prairies. Approximately once per 3.5 years, the Vermillion runs dry.