Abu Anas al-Libi, 50, was on the FBI's most-wanted list with a $5 million price on his head when he was captured by US troops in the Libyan capital Tripoli in October 2013.
He and Saudi businessman Khalid al-Fawwaz were due to stand trial on January 12 over the attacks in Kenya and Tanzania that killed 244 people and wounded more than 5,000.
But Libi, a computer expert, died at a hospital in the New York area on Friday, his lawyer Bernard Kleinman told The Washington Post, saying the health of his client -- who had advanced liver cancer -- had deteriorated significantly in the last month.
Libi and Fawwaz both previously pleaded not guilty to conspiracy charges.
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A third suspect, Egyptian Adel Abdel Bary, last year pleaded guilty to playing a role in the 1998 attacks.
Libi, who also suffered from hepatitis C, told a federal court in Manhattan in October that he had been on hunger strike when questioned by FBI agents -- during which he made an incriminating statement.
Looking pale and thin, and speaking very quietly through a translator, Libi told the court that he told "anyone who asked" that he was on a hunger strike.
He was detained by US commandos on October 5, 2013 and interrogated on board a US warship before being handed over to FBI agents on October 12.