Van Dijk missed a large chunk of last season through injury, and his return to the team was delayed following a summer of speculation regarding his future.
The Dutchman expressed his desire to leave the Saints amid interest from Liverpool, but he has now been welcomed back into the fold alongside Maya Yoshida at the heart of the defence.
It is the only change made by the visitors from the team that narrowly lost to Manchester United last weekend, with Shane Long again leading the line while Manolo Gabbiadini has to make do with a place on the bench.
The Saints have failed to score in four of their six league games this season, but they come up against a Stoke side winless in five outings.
Mark Hughes's side are boosted by the returns of Kurt Zouma, Geoff Cameron and Kevin Wimmer, though, all of whom were absent for last weekend's 4-0 defeat to Chelsea through a mixture of injury and ineligibility.
The 24-year-old makes just his second league start of the season, replacing Jese Rodriguez in the side.
Stoke City: Butland; Zouma, Cameron, Wimmer; Diouf, Allen, Fletcher, Pieters; Shaqiri, Choupo-Moting; Berahino
Subs: Grant, Johnson, Tymon, Afellay, Adam, Crouch, Ramadan
Southampton: Forster; Cedric, Van Dijk, Yoshida, Bertrand; Romeu, Lemina, Tadic, Davis, Redmond; Long
Subs: McCarthy, Hoedt, Hojbjerg, Ward-Prowse, Boufal, Gabbiadini, Austin
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