Coverage: Live commentary on BBC Radio 5 live, the BBC Sport website and app; watch highlights on BBC Two, BBC iPlayer and online from 19:30 GMT. He will re-join the squad on Sunday.
Ashton is back in the worldwide fold for the first time in four years.
England coach Eddie Jones sprung a surprise by naming Mark Wilson at number eight for Saturday's test against South Africa as he opted for a new-look back row combination boasting only six global starts between them. The action starts on Saturday, November 3 against South Africa before clashes against New Zealand, Japan and Australia.
With the Springboks' European-based players unavailable, full-back Damian Willemse makes his full debut. He missed the start of the campaign through suspension.
If the 31-year-old does come on as a finisher it will be his first England cap in four years, as he last played on the 2014 tour of New Zealand.
England: Elliot Daly; Jack Nowell, Henry Slade, Ben Te'o, Jonny May; Owen Farrell (co-capt), Ben Youngs; Mark Wilson, Tom Curry, Brad Shields; George Kruis, Maro Itoje; Kyle Sinckler, Dylan Hartley (co-capt), Alec Hepburn.
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"Whenever South Africa play, whether it's U20s or the senior side there is always that physical challenge". "But this is still a Springbok side on the rise and a fierce opener for England's autumn series".
Chris Ashton has been drafted in as Tuilagi's bench replacement.
"We've become very well organised in our set-piece and have done a lot of good work in Portugal over the last week", Jones said. "We have put in a new defence system and our attack looks more organised than it was on the South Africa tour", Jones said on the England team website.
South Africa have won 13 of the last 16 meetings, drawing one and losing two.
Dylan Hartley and Owen Farrell are both named as co-captains with Jack Nowell returning to the starting XV after a nine-month absence.