US media outlets said the man knew one of the Boston bombers and was shot by an FBI agent in the early morning incident in Orlando, Florida.
The Federal Bureau of Investigation said the man initiated a "violent confrontation" during the questioning and was killed and that an FBI agent suffered "non-life threatening injuries."
The FBI did not name the killed man, but the Orlando Sentinel newspaper identified him as Ibragim Todashev, 27.
The man was being questioned by the FBI agent, two Massachusetts state troopers and other law enforcement personnel, the FBI said in a statement. It gave no other details.
Tsarnaev, 26, and his brother Dzhokhar, 19, were the alleged perpetrators of the April 15 Boston Marathon bombing that killed three people and wounded more than 260 near the finish line of the race.
Tamerlan Tsarnaev died in a shootout with police. His brother was captured after an exhaustive manhunt and is in custody.
Today Todashev allegedly attacked an FBI agent with a knife, broadcaster NBC reported, adding that he had spent time in the Boston area but was not suspected of having played any part in last month's attack.
Khusn Taramiv, a friend of Todashev's, told local broadcaster WESH that Todashev had lived in Boston and, like the older Tsarnaev, practiced martial arts.
He added that Todashev spoke briefly by phone with Tsarnaev last month and that the FBI had expressed interest in him since the bombings.
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