Fijian-born Hughes, 25, qualified to play for England this year after three seasons with Premiership club Wasps.
Number eight Josh Beaumont, son of former England captain Bill, was included after being named in this year's Six Nations squad but missing the tournament due to injury.
Flanker Michael Williams, scrumhalf Dan Robson and centres Ben Te'o and Joe Marchant are the other uncapped players in the squad.
Number eight Ben Morgan, who has played 31 tests, was called up by Jones for the first time.
"With a number of players missing through injury it's a good opportunity for others to put their hands up and show us what they're made of," Jones said.
"I think it's a good situation to be in. Injuries allow us to strengthen the depth of our squad and develop robustness. Ideally, by the Rugby World Cup in 2019, we're looking to have three players in every position who are interchangeable."
England, unbeaten since Jones took charge after last year's World Cup, host South Africa, Fiji, Argentina and Australia in November and December. The final squad for the Autumn internationals will be announced on Oct. 26.
Forwards: Josh Beaumont (Sale Sharks), Dan Cole (Leicester Tigers), Jamie George (Saracens), Teimana Harrison (Northampton Saints), Dylan Hartley (Northampton Saints), James Haskell (Wasps), Paul Hill (Northampton Saints), Nathan Hughes (Wasps), Maro Itoje (Saracens), Sam Jones (Wasps), George Kruis (Saracens), Joe Launchbury (Wasps), Courtney Lawes (Northampton Saints), Joe Marler (Harlequins), Ben Morgan (Gloucester Rugby), Chris Robshaw (Harlequins), Tommy Taylor (Wasps), Billy Vunipola (Saracens), Mako Vunipola (Saracens), Mike Williams (Leicester Tigers);
Backs: Mike Brown (Harlequins), Danny Care (Harlequins), Elliot Daly (Wasps), Ollie Devoto (Exeter Rugby), Owen Farrell (Saracens), George Ford (Bath Rugby), Alex Goode (Saracens), Jonathan Joseph (Bath Rugby), Joe Marchant (Harlequins), Jack Nowell (Exeter Chiefs), Dan Robson (Wasps), Semesa Rokoduguni (Bath Rugby), Henry Slade (Exeter Chiefs), Ben Te'o (Worcester Warriors), Anthony Watson (Bath Rugby), Marland Yarde (Harlequins), Ben Youngs (Leicester Tigers).
(Reporting by Ian Rodricks in Bengaluru, editing by Ed Osmond)
