The poll has been triggered by the resignation of Tory MP Zac Goldsmith in protest at the government's backing for a third runway at Heathrow.
Mr Goldsmith, who will run again as an independent, has said it "must be a referendum on Heathrow expansion".
But the likely Lib Dem candidate said Mr Goldsmith's backing for Brexit would be "uppermost in voters' minds".
Sarah Olney, who has already been selected to fight the seat at the next General Election, said it was a "farce" the by-election was taking place, saying it was the result of Tory in-fighting but added that the Lib Dems were looking forward to "putting our message in front of voters".
Ms Olney, who like Mr Goldsmith is opposed to Heathrow expansion, told the BBC's Daily Politics: "We are on the same side as far as Heathrow is concerned, so for the voters to be able to choose between us, it's going to be fought on other issues - and I think Brexit is currently going to be the main issue that's uppermost in voters' minds."
A local breakdown of the EU referendum results shows almost 70% of voters in the Richmond council area, which makes up the bulk of the constituency, backed Remain.
Ms Olney is expected to be confirmed as the party's pick for the by-election after party leader Tim Farron rejected the idea of parachuting in one of its big names.
The Conservatives are not fielding a candidate against Mr Goldsmith, who held the south-west London seat in 2015 with a 23,015 majority. The Lib Dems, who held the seat until 2010, finished second.
Labour says it will field a candidate despite three of its MPs urging it to consider standing aside to maximise the chances of a Tory defeat.
The Green Party said it was also likely to put forward a candidate although it said it supported "progressives working together to beat the Conservatives".
In standing down, Mr Goldsmith - who has long campaigned against a third runway -  fulfilled a pledge to quit if the government backed the expansion.
He said: "There was no small print, no expiry date, no ambiguity. It was a simple promise. And it mattered.
"I know it mattered, because the thought of Heathrow expansion fills most of my constituents with dread."

It comes after shopkeepers claimed their trade was being affected by the abuse of regulations.
They have blamed the removal of the police traffic warden service more than two years ago.
A council report on the possibility of introducing its own wardens will be considered next month.
Councillors were told this week that the impact of the removal of the old service had not been as big as was generally perceived.
It was claimed parking habits had "not actually changed significantly".
However, a petition from regeneration group Future Hawick said there had been a "marked increase in the abuse of parking regulations".
Now letters will be sent out reminding people in the area of the parking regulations and notices put up in Hawick Town Hall encouraging staff and visitors to use off-street parking.
Councillor Alec Nicol said a full report on the issue of on-street parking would be considered next month.
"There are some things that could be done immediately which may alleviate some of the issues in the short term," he added.
The Liberal Democrats have vowed to make the Richmond Park by-election about Brexit, not Heathrow.
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Letters are to be sent to businesses and residents on Hawick High Street reminding them of the 30-minute parking limit in the area.