Hernando is a city in and the county seat of DeSoto County, which is on the northwest border of Mississippi, United States. The population was 14,090 at the 2010 census, up from 6,812 in 2000. DeSoto County is the second-most-populous county in the Memphis metropolitan area.U.S. Route 51 and the I-55 freeway traverse the city from north to south, and the I-69 freeway crosses the city from east to west. Hernando's historic downtown square, which surrounds the county courthouse, is located at the intersection of Commerce Street and what is now U.S. 51.