Updated 9.08pm -

Spain's northeastern region of Catalonia failed to hold an independence referendum, Prime Minister Mariano Rajoy said, after more than 760 people were injured in clashes between police and voters during a ballot Madrid said was illegal.

The people of Catalonia had been tricked into taking part in the banned vote, Rajoy said, adding that the referendum was a strategy by the regional government against legality and democratic harmony and was a "path that leads to nowhere."

Rajoy thanked security forces for upholding the law and doing their job.

He also called to meet with all Spanish political parties to discuss the country's future following the referendum.

During the day, Spanish riot police burst into polling stations across Catalonia, confiscating ballot boxes and voting papers to try to halt the banned referendum on a split from Spain as Madrid asserted its authority over the rebel region.

Police broke down doors to force entry into voting stations as defiant Catalans shouted 'Out with the occupying forces!" and sang the anthem of the wealthy northeastern region. In one incident in Barcelona, police fired rubber bullets.

Officers in riot gear forcibly removed people from a polling station in Girona and Catalan firefighters protected voters by standing between them and national police.

Catalonia's health department said 760 people had been treated due to clashes with police forces.

Catalan regional leader Carles Puigdemont accused Spanish authorities of using "unjustified, disproportionate and irresponsible" violence.

"The unjustified, disproportionate and irresponsible violence of the Spanish state today has not only failed to stop Catalans' desire to vote ... but has helped to clarify all the doubts we had to resolve today," he said.

The referendum, declared illegal by Spain's central government, has thrown the country into its worst constitutional crisis in decades and deepened a centuries-old rift between Madrid and Barcelona.

Despite the police action, hundreds-strong queues of people formed in cities and villages throughout the region to cast their votes. At one Barcelona polling station, elderly people and those with children entered first. The result will be known in the coming days.

"I'm so pleased because despite all the hurdles they've put up, I've managed to vote," said Teresa, a 72-year-old pensioner in Barcelona who had stood in line for six hours.

The ballot will have no legal status as it has been blocked by Spain's Constitutional Court and Madrid for being at odds with the 1978 constitution.

A minority of around 40 percent of Catalans support independence, polls show, although a majority want to hold a referendum on the issue. The region of 7.5 million people has an economy larger than that of Portugal.

However much voting takes place, a "yes" result is likely, given that most of those who support independence are expected to cast ballots while most of those against it are not.

Organisers had asked voters to turn out before dawn, hoping for large crowds to be the world's first image of voting day.

"This is a great opportunity. I've waited 80 years for this," said 92-year-old Ramon Jordana, a former taxi driver waiting to vote in Sant Pere de Torello, a town in the foothills of the Pyrenees and a pro-independence bastion.

The Catalan government said voters could print out ballot papers at home and lodge them at any polling station not closed down by police. 

Nicola Sturgeon, the leader of Scotland, which voted to remain part of the United Kingdom in a 2014 referendum, said she was concerned by the images she was seeing from Catalonia.

"Regardless of views on independence, we should all condemn the scenes being witnessed and call on Spain to change course before someone is seriously hurt," she said on Twitter.

Belgian Prime Minister Charles Michel tweeted: "Violence can never be the answer! We condemn all forms of violence and reaffirm our call for political dialogue."

'I'VE WAITED 80 YEARS'

"This is a great opportunity. I've waited 80 years for this," said 92-year-old Ramon Jordana, a former taxi driver waiting to vote in Sant Pere de Torello, a town in the foothills of the Pyrenees and a pro-independence bastion.

He had wrapped his wrists in Catalan flags, among 100-150 people who gathered at a local school that had been listed as a polling station, ready to block any police from entering. A tractor also stood guard, though no police had yet arrived.

Leading up to the referendum, Spanish police arrested Catalan officials, seized campaigning leaflets and occupied the Catalan government's communications hub.

But Catalan leaders urged voters to turn out in a peaceful expression of democracy. Families occupied scores of schools earmarked as voting centres, sleeping overnight in an attempt to prevent police from sealing them off.

Around 70 polling stations were raided by police, Spanish Interior Minister Juan Ignacio Zoido said.

The aim of the raids was to seize referendum material and not to target people wanting to vote, another senior government official said.

Spain's Deputy Prime Minister Soraya Saenz de Santamaría said police had acted in a proportionate manner.

"We have been made to do something we didn't want to do," said Enric Millo, the central government's representative in Catalonia, at a news conference.

One analyst said the scenes being played out across Catalonia would make it harder for Madrid and Barcelona to find a way forward.

"I think it is going to make the clash more intense and make it more difficult to find a solution," said Antonio Barroso of Teneo Intelligence.

Puigdemont originally said that if the "yes" vote won, the Catalan government would declare independence within 48 hours, but regional leaders have since acknowledged Madrid's crackdown has undermined the vote.