"I want to be clear: it will not succeed if it does not guarantee that the standards we have in France for our citizens' health and environment will be maintained," Valls said at a government-organised environmental conference in Paris on Tuesday. "And today we are too far from that to envisage an agreement."
US President Barack Obama this week visited Europe, in part to push the free-trade deal, which has been opposed by civil society groups who claim that negotiations have been hidden from public view and that it could harm agriculture and the environment.
Earlier on Tuesday French Foreign Trade Minister Matthias Fekl, who leads negotiations for France, predicted that the deal would not be signed before the end of Obama's mandate at the end of the year and raised the possibility that agreement may never be reached.
"We're getting further away from the chance, or risk - people will make their own minds up - of any conclusion at all,' he told RTL radio.
Negotiations have been going on since 2013 and campaigners have raised concerns that it will allow companies to challenge national legislation in court, including on such key questions as health and the ecology.
"I don't see Europe having to follow the US," Fekl said. "The world's biggest economic grouping is Europe, the biggest grouping in value and weight in world trade is Europe. Europe should make its own voice heard."
Earlier this month President François Hollande said that France "could still say no" if conditions on transparency and access to public contracts were not acceptable.