Ashya King's family took him from Southampton General Hospital on Thursday afternoon and travelled on a ferry to France some two hours later.
Assistant Chief Constable Chris Shead of Hampshire Constabulary said the boy's parents Brett King, 51, and Naghemeh King, 45, had been arrested at 10pm local time after Spanish police stopped the family's vehicle.
"We don't have many details on Ashya's condition at this point in time but what we do know is that he was showing no visible signs of distress," Mr Shead said.
"Ashya has now been taken to a hospital in Malaga. The parents have been arrested. They have been taken to a police station."
Hampshire Police has said Ashya King should be re-united with his parents at a "difficult and scary" time for him during his treatment.
A British mother whose son's life was saved by proton therapy has told ITV that she defied NHS doctors' advice to pursue the treatment.
The parents of Ashya King said they took him out of a hospital to seek proton beam treatment which is not available under the NHS.