Wilshere is joined in the team by Bournemouth midfielder Lewis Cook, who is one of four uncapped players alongside Burnley duo Nick Pope and James Tarkowski and Swansea City's Alfie Mawson.
The omission of Cahill, who recently lost his place in the Chelsea side, means there are no Blues players in boss Southgate's squad for the games against the Netherlands and Italy.
Southgate said on Wilshere: "Jack's a player that has unquestionable talent".
Danny Rose and Dele Alli hobbled out of Tottenham's most recent game, but both are named in the squad, unlike team-mate Harry Kane who is out of action until next month with an ankle issue.
Southgate names his squad for the forthcoming friendlies against Holland and Italy as preparations intensify for the World Cup. "Gary can still make the World Cup if he is playing".
"And the only thing at this stage that is of highest importance is the safety and security of our players and absolutely of our travelling supporters".
'Now he's playing the matches that matter for Arsenal and playing well.
He added: "I think the medical reports we have are that for sure he'll play well before the end of the season".
"Always part of what I'm working on is the strength of the squad and people are able to come in", said Southgate.
"And in those other matches, the likes of Daniel Sturridge, Marcus Rashford and Jamie Vardy have all stepped forward and scored important goals - and Jermain Defoe".
'We want to keep him involved but there's good competition for places'. The FA is aware that the manager will also have to discuss the ongoing crisis and whether England should boycott the tournament.
Ronald De Boer wades into spat between brother Frank and Jose Mourinho
I said that before the Liverpool match when many of you were maybe not expecting him to start. Sometimes you are in the team, sometimes you are not in the team.
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