Hampshire Constabulary has confirmed there is positive information to suggest the family of Ashya King may now be in Spain.
The police force said it now has information which suggests the family has strong links to the Marbella area and that they may be travelling there.
The family's car was spotted on Friday, according to police, which has shifted the focus of the search to Spain.
Officers are now working with Spanish authorities in a continued effort to locate the missing five-year-old, who has a brain tumour.
Five-year-old Ashya needs treatment for a brain tumour Assistant Chief Constable Chris Shead said: "The need to find Ashya is now desperate. It is really important that we find him and ensure he receives medical attention at the earliest opportunity.
"We still don't know whether the King family has any spare batteries for the machine which administers food, the knowledge, or any way of recharging the battery. Without properly administered food Ashya's situation is very serious.
"We have information to suggest that the family may well be on the way to Spain and our search is concentrating on the Marbella area.
Ashya was taken from the hospital by his parents Brett and Naghemeh "I do have to stress although that's what we're focusing our attention at this point in time, they could equally be anywhere and we would urge anybody on the continent to stay vigilant, keep your eyes open, and if they see the vehicle they're travelling, if you see the family or indeed if you see Ashya please contact police."
Mr Shead added officers would be contacting hospitals across Europe, looking for someone matching the little boy's description or symptoms to see if he has been admitted.
Ashya's family took him from Southampton General Hospital, where he was receiving treatment, at around 2pm on Thursday and travelled on a ferry to Cherbourg, France, two hours later.
Interpol has issued a yellow alert in 190 countries The little boy is in a wheelchair and is being fed through a tube. He has undergone "extensive surgery" - with his last operation seven days ago.
Police were told by the hospital that the little boy was missing at 8.35pm that day - more than six hours after he was taken by his parents - Jehovah's Witnesses Brett King, 51, and Naghemeh King, 45.
The family, from Southsea, is travelling in a grey Hyundai I800 Style CRDI registration KP60 HWK.
Interpol has sent out a missing persons alert to its 190 member countries as concerns for the boy's welfare have grown.
Ashya is likely to be in a wheelchair or buggy, cannot communicate verbally and is immobile, a police spokesman said.

University Hospital Southampton NHS Foundation Trust said Ashya was allowed to leave the ward under his parents' supervision and hospital staff raised the alarm when his absence "became a cause of concern".
Legal experts have said that it is "unlikely" that the Kings had committed an offence by taking Ashya out of hospital.
A post on Hampshire Constabulary's Facebook page said: "This is my mother's friend, she has run away in desperation because they cannot accept that there is nothing that can be done for their son and want to look for help abroad.
"Please don't judge, they are a very sweet loving family and I can only believe they are doing this because they want to help their son."
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