The Three Lions skipper has been declared fit to play and returned to training on Wednesday. Kane suffered an ankle knock early in the second half of England's 6-2 win over Iran, though he is ready to step back into action against USA.
When asked about his star forward, Southgate said: "Harry is fine. He has worked slightly separately from the group but all good for Friday night.
"He had a scan [on Wednesday] to make sure everything is fine."
The Tottenham ace has scored 51 goals in 76 England appearances and finds himself just two behind record goalscorer Wayne Rooney.
Kane is expected to feature on Friday as he looks to close the gap on the current DC United manager.
Another man hoping to play a part is Manchester United defender Harry Maguire.
The 29-year-old was substituted during Monday's opener against Iran, though Southgate revealed his player is feeling 'much better'.
"He was feeling ill and that was affecting his vision," Southgate told BBC Sport. "You worry about concussion in that instant, but we were going back through all the footage and there is nothing, so he is in a good area."
Kyle Walker has returned to training, giving Southgate an extra defensive option ahead of a crucial Group B clash with the United States.
England could seal progression to the knockout stages with victory over the Americans on Friday.
"We would like to get qualification done as soon as possible," said Southgate. "The first objective is to get out of the group.
"We would love to do that on Friday, but the game won't be anything like Monday.
"We have to make sure we are back to the psychological place we were at the start because the States will be an athletic team, press really well, be organised, well coached.
"They have quite a few players we know from the Premier League and they showed in the first half against Wales the best side of themselves.
"Monday was a great start and it is that reset to be ready for Friday."