Hernando is a city in central DeSoto County, Mississippi, United States. The population was 14,135 at the 2010 census. Hernando is the county seat of DeSoto County, 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 traverse the city east to west and north to south. Hernando's historic downtown square, which surrounds the county courthouse, sits at the intersection of Commerce Street and U.S.