Ukrainian opposition leader and boxer Vitali Klitschko on Tuesday said the president would face pressure to resign if Kiev fails to secure a landmark EU deal this year.
The WBC world heavyweight boxing champ dubbed "Dr Ironfist" is himself considering a run for the top job in 2015.
"If the association agreement (is) not signed, it means the fall of (the) government and President (Viktor) Yanukovych," Klitschko told AFP on Tuesday.
The 42-year-old spoke on a visit to Lithuania, the current holder of the European Union's half-year rotating presidency.
"After such a disaster, there would be only (one) way (out) for President Yanukovych -- to resign," he said.
To move forward, "there is just one way -- to change power in Ukraine."
Ukraine is gearing up to sign a free trade and association agreement with the EU at a November summit in Lithuania, a move fiercely opposed by Soviet-era master Russia, which still sees the country of 46 million people as firmly within its sphere of influence.
Kiev's imprisonment of firebrand ex-prime minister Yulia Tymoshenko, sentenced in October 2011 to seven years in jail on abuse of power charges, remains a key obstacle to the deal.
Believing her jail term has political overtones, the EU has consistently called for Tymoshenko's release before the deal is finalised.
"If President Yanukovich really wants to provide European integration for Ukraine, he will release Tymoshenko," Klitschko said.
The leader of the democratic reform UDAR (Punch) party also dismissed Russian pressure on Kiev against the EU deal.
"Russians try to suggest an idea: 'You are with us, or against us'. We are for Ukraine! We are just for (a) new level of values where human rights are at the top," he said.
Klitschko had backed pro-West former president Viktor Yushchenko against the Moscow-backed Yanukovych during Ukraine's heady 2004 Orange Revolution.
The boxer on Monday reiterated that he may run against Yanukovych in the 2015 election but said solid support from all opposition parties was key to his decision.
He said he wants to tackle rampant corruption and bring Ukraine into the "European family."
He hinted he would reveal his future plans after Saturday's long-anticipated bout between his younger brother Wladimir, who holds four heavyweight world titles, and Russia's Alexander Povetkin.
"We are looking now for Wladimir Klitschko's fight and after that we can say a little bit more about my career."