The Pope was "profoundly saddened" by the news, his spokesman Francesco Lombardi said.
Before becoming Pope Francis, Jorge Mario Bergoglio was cardinal of Buenos Aires.
His nephew's family was reportedly returning home from a break when their car collided with a lorry at James Craik, some 580km (360 miles) north-east of Buenos Aires shortly before midnight.
The Papal spokesman said he asked "all who share in his grief to unite with him in prayer".
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