The Tottenham striker, 25, who scored six goals and won the World Cup in the summer, has started 61 matches in all competitions since the start of last season.
"I think this is a good opportunity to do it," Southgate said.
Kane's Spurs team-mate Dele Alli has withdrawn from the squad with a minor muscle strain.
England face in Leicester after three straight defeats.
As many as nine changes are expected from the side that started the 2-1 Nations League loss to Spain, with Eric Butler, Ruben Loftus-Cheek, Fabian Delph, James Tarkowski and Danny Welbeck.
"Harry falls into the category in which we have several players," said Southgate.
I'm sure I would have come back sooner than I am sure everybody would have come for club matches, although that is entirely understandable.
"We talked a bit after the World Cup about the demands of the modern player." Everybody has got to play in that but the clubs own the player and they have got to do the right thing for themselves. "
Southgate has brought in Leicester's Ben Chilwell and Demarai Gray from the Under-21s for the Switzerland game
Left-back Chilwell, 21, and forward Gray, 22, could both make international debuts on their home ground.
Manchester United defender Luke Shaw left the camp early following the concussion he suffered in a nasty collision with Spain's Dani Carvajal at Wembley on Saturday.
He had reported to St George's Park for monitoring but was released
England's defeat by Spain was their first match since losing the third-place play-off match to Belgium at the World Cup finals in Russia.
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