Muammar Gaddafi's spokesman told Reuters on Saturday that NATO air strikes on Sirte overnight had hit a residential building and a hotel, killing 354 people.
His claim could not immediately be verified as Sirte, Gaddafi's hometown, has been largely cut off from communication since the fall of Tripoli.
NATO comment was not immediately available.
Moussa Ibrahim, in a call from a satellite phone to Reuters office in Tunis, said: "NATO attacked the city of Sirte last night with more than 30 rockets directed at the city's main hotel and the Tamin building, which consists of more than 90 residential flats.
"The result is more than 354 dead and 89 still missing and almost 700 injured in one night."
Ibrahim said Gaddafi was personally directing loyalist fighters who are holding back provisional government forces at his remaining strongholds in Libya.
"He is leading all aspects of this struggle. He is talking to the people, he is lecturing, he is discussing, he is looking after all matters of the resistance," he said.
Ibrahim said Gaddafi was in Libya and confident of victory.
"We will be able to continue this fight and we have enough arms for months and months to come," he said.
"In the last 17 days more than 2,000 residents of the city of Sirte were killed in NATO air strikes," he said.