England eye Euro 2020 last 16 by breaking Scotland hearts
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"For the fans and for us it is a big occasion but it is another opportunity for three points and our objective is qualification. That is what we have got to focus on," said Southgate at his pre-match press conference.
"I want them to approach it like any other game of football and focus on playing well and don't need to emphasise the other parts too much."
Despite having just 2,500 tickets for the 22,500 crowd limited by coronavirus restrictions, Scottish fans have already descended on London in their thousands.
After a 23-year wait to reach a major finals, the Scots were stung by Patrik Schick's stunning strike to lose 2-0 to the Czech Republic on Monday.
Another defeat would leave Steve Clarke's men needing to beat World Cup finalists Croatia heavily in their final game and other results to go their way to have any chance of reaching the knockout stage for the first time.
- Tierney returns -
Scotland's chances of causing an upset have received a massive boost with the return of Arsenal defender Kieran Tierney from a hamstring injury.
"We need him back. He's a top player and an amazing character and someone we want back in the team," said Manchester United midfielder Scott McTominay.
"He's someone we need and we rely on him a lot for what he brings to the squad."
England also have a full compliment of players to choose from with United captain Harry Maguire back in contention after recovering from ankle ligament damage.
Southgate's men avenged their World Cup semi-final defeat by Croatia to get off to a winning start in the European Championship for the first time on Sunday.
Croatia will look to bounce back when they face the Czechs in Glasgow in Friday's 1600GMT kick-off.
Slovakia were the only side in Group E to get off to a winning start as they beat Poland 2-1 and could also secure a place in the knockout stages with victory over Sweden in Saint Petersburg (1300GMT).
The Swedes' ultra defensive approach against Spain in their opening match was heavily criticised, but despite enjoying just 25 percent possession they escaped with a 0-0 draw in Seville.
- De Bruyne leads Belgium -
Belgium and the Netherlands joined the Italians in the knockout stages with victories on Thursday.
In a match laced with emotion following Christian Eriksen's cardiac arrest in Denmark's 1-0 defeat to Finland on Saturday, Belgium came from behind to win 2-1 in Copenhagen.
Kevin De Bruyne came off the bench to tee up Thorgan Hazard to cancel out Yussuf Poulsen's early opener before the Manchester City midfielder drilled home the winner.
The match was paused after 10 minutes -- a reference to Eriksen's number 10 -- for a minute's applause.
The Netherlands secured top spot in Group C with a routine 2-0 win over Austria thanks to goals from Memphis Depay and Denzel Dumfries.