Police said the van's driver had been ordered to move his vehicle because it was double parked on 34th Street, a midtown thoroughfare filled with tourists and shoppers during the holidays.
The van abruptly moved forward, striking several pedestrians, before it crashed into the back of a bus, police said.
Four people died at the scene after the evening rush hour accident. Two others died in a hospital. The condition of the other victims was not immediately known.
A witness said the van hit pedestrians in the crosswalk before striking the bus, and that some people were trapped between the two vehicles.
M.S. Thapa said the bus had been trying to make a right turn before the accident in Herald Square, and that he heard screams and a crash as the van hit the bus.
One of New York's prime shopping destinations, Herald Square hosts Macy's flagship store and is known by television viewers nationwide as the terminus of Macy's annual Thanksgiving Day Parade.
Such city landmarks as the Empire State Building and Madison Square Garden are just blocks away.
The van's driver, identified only as a 77-year-old man, was being questioned by police.
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