At least 460 people have been injured in clashes as police try to stop Catalonia's illegal independence poll, authorities say.
The figure came from Barcelona's mayor Ada Colau, who demanded an end to "police actions against a peaceful defenceless population".
Branding Spain's prime minister "a coward...hiding behind thousands of police" she called for Mariano Rajoy to resign or be removed from office.
Riot officers fired rubber bullets - which are banned in Catalonia - and used batons on crowds protesting in Barcelona on Sunday, sending people running for cover.
Police vans drove down the road as protesters who had been sitting on the street fled, and witnesses said some people were bleeding.
Spain's Interior Ministry said 12 police had been injured and three people, including one young girl, had been detained for disobedience and assaulting a police officer.
Deputy prime minister Soraya Saenz de Santamaria said officers had acted professionally and proportionately.
Sky News Europe Correspondent Mark Stone, who was at the scene, collected one of the large ball projectiles, which he said were "pretty hard".
He said it was unclear whether there was any spark that caused police to act over what appeared to be a largely peaceful protest.
He said: "It has been chilling. I have seen riot police in action in many parts of the world. Normally riot police are dealing with riots.
"These were people carrying out what they believe was their democratic right - going into polling stations peacefully, putting a mark on a peace of paper and putting it in a box.
"And for doing that, in the European Union, police were pulling them out by their hair...they were being stamped upon they were being thrown to one side - and then rubber bullets being used to disperse them."
Emergency services said most of the people hurt had minor injuries such as "bruises, dizziness and anxiety attacks". However there also said to be some serious injuries.
People in the northeastern Spanish region have turned out in large numbers for the illegal referendum on splitting from Spain - but police have blocked off polling stations and forcibly seized ballot boxes.
Just outside Girona, to the north of Barcelona, police used a hammer to smash through a glass door of a school where Catalonia's president, Carles Puigdemont, was expected to appear.
There were scuffles outside as people chanted: "I will vote!
Mr Puigdemont called the crackdown "unjustified, disproportionate and irresponsible" and said it showed a "dreadful external image of Spain".
But the top government official in the region, Enric Millo, said police were acting "professionally" to enforce the constitutional court's ruling.
"Today's events in Catalonia can never be portrayed as a referendum or anything similar," he added.
Catalan officials said voters could go to any polling station, not just their designated one, in an attempt to ensure people could vote.
The regional government tweeted on Sunday morning that 73% of polling stations (4,561) were open. By mid-afternoon, Spain's Interior Ministry said 92 polling stations had been closed.
One man, voting with his grandparents in Barcelona, told Sky News it was massively important for them to have their say because they had lived through General Franco's dictatorship - which tried to stifle the Catalan culture and language.
Spain's interior ministry has tried to disrupt the vote by disabling the website hosting census data .
Barcelona's Spanish league game against Las Palmas was played behind closed doors amid the tensions - with the word "democracia" displayed on the scoreboard.
The club made the announcement with just half an hour to kick-off and said the league had refused a request for the game to be postponed.
It said it meant that people could now vote at several polling stations and "regardless of origin or place of residence".
On Saturday night, campaigners camped out in schools, many with their children, in an attempt to stop police taking over the buildings.
The government's assertion that the referendum is illegal is backed up by the courts and a judgment based on the Spanish constitution.
Many in Catalonia and across Spain do not support the illegal vote or the push for independence and protests have been held in recent days in cities including Barcelona and Madrid.
British politicians have also weighed in on the events in Catalonia.
Jeremy Corbyn tweeted: "I urge @Theresa_May to appeal directly to Rajoy to end police violence in Catalonia & find political solution to this constitutional crisis."
SNP leader Nicola Sturgeon posted: "Increasingly concerned by images from #Catalonia. Regardless of views on independence, we should all condemn the scenes being witnessed."
A UK Foreign Office spokesperson said: " The referendum is a matter for the Spanish Government and People. We want to see Spanish law and the Spanish constitution respected and the rule of law upheld.
Spain is a close ally and a good friend, whose strength and unity matters to us."