Catalans have clashed with Spanish riot police, as the referendum in the region began.
The Spanish national police began seizing ballot boxes and voting papers from Catalan polling stations, the Interior Ministry said.
It can be recalled that the referendum is unaccepted to the Spanish government, and it have tried to stop it.
There have been reports of scenes at polling stations with bleeding faces of voters.
Some people who attempted to vote and fought with riot police were taken away in ambulances after being injured.
At another polling station, would-be voters chanted "we are people of peace" and "we are not afraid". Half a dozen armoured police vans and an ambulance stood ready nearby, the witness said.
Catalans were defying rain and police orders to leave designated polling booths as the referendum got under way on the region's secession that has challenged Spain's political and institutional order.
Organisers have asked people to block entrances and use passive resistance during voting, which started 9am (07:00GMT).
Spanish riot police smashed their way into a polling station in Sant Julia de Ramis, near the Catalan city of Girona, where Catalan President Carles Puigdemont was expected to vote.
Civil Guard officers with shields used a hammer to smash the glass of the front door and lock cutters to force their way in. Scuffles erupted outside between police and people waiting to vote.