Flames erupted on the sixth floor of 72 Columbia St., near Rivington Street, at about 11:50 p.m., seriously injuring a man, whose name and age were not released, officials said.
The man was rushed to New York Hospital, the fire spokesman said.
"I came out of the apartment to see what was going on. I looked back out the window and saw a man on the stretcher. Firefighters were standing over him. They were moving fast," said Nilda Cruz, 62, who lives on the eighth floor.
Neighbors described the man as kind, but said he didn't go out of his way to make friends.
"I saw him two days ago," said Carmen Velez, 69, who lives on the 19th floor. "He would say, 'Good morning' and told me how beautiful I looked."
"I feel so bad for him. Nobody deserves this," Velez added.
It wasn't immediately clear what sparked the blaze, but fire marshals are investigating, officials said.