Alfredo Palacio also accused the thousands of protesters gathering in the cities of trying to topple his government.
Police fired teargas to disperse the Indians who have blocked roads with burning tyres and rubble in eight central provinces since Monday.
Palacio said in a pre-recorded statement broadcast late on Wednesday: "The free-trade deal is in the middle of negotiations and the Ecuadorean government cannot assume any compromise to sign it or not while there are still issues to be resolved."
The protests were a "political imposition aimed to dissolving the nation", Palacio said.
However, he promised to revive plans for a referendum to rewrite the constitution as a way out of the political crisis. His previous attempts at reform have been repeatedly stymied by congress.
Alfredo Castillo, the interior minister, resigned after making remarks in support of the protesters, who pose the biggest challenge to Ecuador's stability since Palacio took office 10 months ago after congress fired his predecessor.
A woman with a cartoon of
George Bush during a protest
Wilfredo Lucero, the president of congress, said: "The country is at a critical situation and we are headed to anarchy."
Three presidents have been toppled by popular and congressional unrest in Ecuador in less than a decade.
The protests are starting to hurt the economy. Basic food deliveries of corn, potatoes and milk have been disrupted in the central provinces where traffic is blocked and Ecuadorean flower farmers are struggling to transport their shipments.
Protesters using sticks fought briefly with security forces and at least one person was injured by a teargas canister, a police spokesman said.
A barricade on the Pan-American
road in Tabacundo
The demonstrations have gathered force as hundreds of Indians walked down from hamlets in the Andes mountains to join the blockades. They say a trade deal will put them at a disadvantage with US farmers and disrupt their culture.
Government officials have promised Indian leaders a series of meetings this week to discuss the impact of the trade pact before negotiations resume in Washington on 23 March. But protesters said the proposals were not enough.
Palacio has struggled with a series of protests and strikes as a presidential election looms in October. Last week, oil contract workers at state oil firm Petroecuador went on strike and briefly curbed the country's vital crude production.
Activists are also demanding the immediate expulsion of Occidental Petroleum Corp, which the government accuses of improperly transferring an oilfield to another company.