Plaid Cymru have said a vote for them at next year's Senedd elections is a vote for Welsh independence as they commit to offering a referendum within their first term - should they win a majority.
The party's leader, Adam Price MS, said devolution is "under attack" and the need to hold a referendum on Welsh independence has been accelerated by Brexit and the possibility of Scottish independence.
Support for Welsh independence group YesCymru surged during the pandemic as their membership grew from just over 2,000 in February to more than 14,000 in November.
Mr Price has previously called the coronavirus crisis a "game changer" for the independence movement.
The Welsh Liberal Democrats have criticised Plaid Cymru's pledge on a referendum, saying "the best future for Wales is within a new UK".
The UK Government would have the final say over whether a Welsh independence vote takes place.
Should a Plaid Cymru Government form as a result of next year's May elections, the party have said they will offer a binary choice referendum on Welsh independence within their first term.
Adam Price will announce the promise on Friday morning at a keynote address in Cardiff.
The party previously commissioned a report which advised that two independence referenda should be held within a ten year time period. The first to gauge the public view and to persuade UK Government to hold a binary referendum.
On Friday, Mr Price is expected to say that devolution is "under attack from Boris Johnson's Conservatives".
"Meanwhile, the demand for another independence referendum in Scotland is becoming unstoppable and by 2025 Scotland could well be an independent country. And Brexit has also given further impetus to the calls for a united Ireland.
"Wales is in real danger of being be left behind as part of a rump United Kingdom, in a new England-and-Wales formation – which would be the ultimate worst of all worlds."
The Welsh Liberal Democrat's Political and Constitutional Reform spokesperson Cadan ap Tomos said that Brexit has "clearly" shown "just how vital it is to keep close ties with our nearest neighbours."
They agree that the current UK union "does not work well enough for Wales" but that means we should reform it - not leave it.
Mr Tomos added: "Don't believe those trying to paint this as a binary choice between independence and same old, same old.
"The best future for Wales is within a new UK – we just need the courage to fight for it."