Appearing on the BBC’s Andrew Marr programme, the Prime Minister was confronted on how he would address a Scottish person who previously supported unionism, but now wanted to leave due to Brexit and his handling of the pandemic.
He said: “Referendums in my experience, direct experience, in this country are not particularly jolly events.
“They don’t have a notably unifying force in the national mood, they should be only once in a generation.”
The PM was also challenged on the difference between a referendum on EU membership being granted and another on Scottish independence being requested.
Mr Johnson suggested there was a significant gap between the EU referendum and that of the United Kingdom European Communities membership.He said: “The difference is we had a referendum in 1975 and we then had another one in 2016.
“That seems to be about the right sort of gap.”
The last referendum on Scottish independence was in 2014.
It came during an interview that also saw the PM suggest tougher measures were set to be brought in to tackle the new variant of the coronavirus.
He said: “It may be that we need to do things in the next few weeks that will be tougher in many parts of the country.
“I’m fully, fully reconciled to that.
“There are obviously a range of tougher measures that that we would have to consider.
"I’m not going to speculate now about what they would be, but I’m sure that all our viewers and our listeners will understand what the sort of things, clearly school closures, which we had to do in March is one of those things.”
Earlier today SAGE member Professor Sir Mark Walport claimed it was "pretty clear" new measures were needed to handle the crisis.
He said: “It’s the Tier 4 restrictions, it’s obeying them.
“It is thinking about breaking essentially every possible route of transmission we possibly can.
“Those are the things that are absolutely necessary and it is pretty clear we’re going to need more.”