"We have really tried our best, but there are risks we cannot reduce," Aubry told a news conference alongside Michel Lalande, the top government official in the region.
Lille's most popular event, held the first weekend of September each year, attracted nearly 2.5 million visitors in 2015.
Cancelling this year's Grande Braderie de Lille was a "painful decision", Aubry said.
Lalande said the decision was necessary because of the "hyper-urban format (of the market) with its streets full of people."
The Lille flea market is the latest event to be called off in a string of cancellations following last month's Bastille Day truck massacre in the Riviera town of Nice that claimed 85 lives following a fireworks display.
Many traditional and cultural festivities have been either downsized or cancelled altogether, with Defence Minister Jean-Yves Le Drian saying the series of jihadist attacks in France put the country in a "war situation".
"Everyone must understand that we are in this situation and that sometimes that entails constraints," he said.
