Robert Kilroy-Silk is "seriously considering" standing in the by-election caused by the nomination of Peter Mandelson as an EU commissioner.
Mr Kilroy-Silk is under pressure to stand
The UKIP MEP said he was "coming under considerable pressure" from the party to run for the Westminster seat.
The pro-euro Lib Dems claim they are in pole position to snatch Hartlepool from Labour.
But Mr Mandelson, who has a 15,000 majority, said he believed Labour could hold on to the seat.
And - although Hartlepool famously elected monkey-suited football mascot Stuart Drummond as its mayor - Mr Mandelson told Sky News the town's people took parliamentary elections "more seriously".
2001 GENERAL ELECTION
Peter Mandelson (Lab) 22,506 (59.15%)
Gus Robinson (C) 7,935 (20.85%)
Nigel Boddy (LD) 5,717 (15.02%)
Arthur Scargill (Socialist Lab) 912 (2.40%)
Ian Cameron (Ind) 557 (1.46%)
Lab maj 14,571 (38.29%) Turnout 56.25%
Conservative co-chairman Liam Fox accused Mr Mandelson of deserting his constituents to take up what he considered a better job in Brussels.
"The people of Hartlepool will punish Labour whenever they are given the opportunity," Dr Fox told BBC News 24.
It is thought the by-election may take place on Thursday, 4 November - but it will not be on the same day as a referendum on a regional assembly for the North-East, which also due to take place in the autumn.
Hartlepool is one of the safest Labour seats in the country, but the party will be taking nothing for granted after the Lib Dems overturned a 13,000 Labour majority in Leicester South earlier this month.
Labour gained an overall majority on Hartlepool council in elections last month and led in votes cast in that contest and the European Parliament election.
In a survey of the results carried out by the Press Association, Labour took 32.5% of the vote, with UKIP in second place on 19.8%, followed by the Conservatives 17%, Lib Dems (13.6%) and the BNP (6.2%).
But Liberal Democrat campaigns manager Lord Rennard said recent local elections in Hartlepool showed his party was a clear contender.
In these, Labour won 31%, Lib Dems 23% and the Tories 12% of the vote.
"Liberal Democrats will be fighting the by-election as the clear challengers to Labour at a time when public trust in Labour is at an all-time low," he said.
UKIP is expected to mount a lavish campaign, bankrolled by its campaign director, the millionaire businessman Paul Sykes.
A UKIP spokesman said it would be targeting the Lib Dem's backing for EU fishing quotas, which he claimed had "destroyed" Hartlepool's fishing industry.
Mr Kilroy-Silk, a former BBC chat show host who resigned following comments about Muslims in a newspaper column, said: "This appointment of Mandelson shows that the European Union is a gravy train for failed politicians.
"He has never been the natural person to represent the people of Hartlepool. Now the prime minister has found him something better to do he is off, without a thought for his constituency.
"If I was a constituent I would feel very used and angry and would want to take my revenge on Labour at the by-election."
The party did not field candidates in Leicester South and Birmingham Hodge Hill, as it was "keeping its powder dry" for the expected Hartlepool contest, a spokesman said.