Police were called to the scene, near a supermarket on Spring Bank, at about 14:00 BST following reports of two pedestrians being hit.
The lorry driver, a 55-year-old man from Hull, has been arrested on suspicion of two counts of causing death by dangerous driving.
Motorists have been advised to avoid the area and the road is closed between Blundells Corner and Princes Avenue.
A mother and her daughter have died after being struck by a lorry in Hull.