WTOK-TV in Meridian reports that the former medical center closed years ago.
The John C. Stennis Memorial Hospital in DeKalb will be owned and operated by Rush Health Systems of Meridian.
The hospital, which is estimated to cost between $10 million and $15 million, will feature 25 beds, an emergency room, administrative offices and a cafeteria.
Officials say construction is expected to take up to a year.
The Mississippi Department of Health issued a certificate of need for the hospital in 2009.