Catalan nationalists want to hold a referendum on whether the region should break away from the rest of Spain.
Polls suggest Catalan nationalist parties are set to do well.
Catalan President Artur Mas called early elections amid a funding row with the central government; it says he is trying to exploit the economic crisis.
Madrid says Catalan nationalists are looking for excuses having nearly run out of money, and having run up a big debt.
Polls close at 20:00 local time.
Artur Mas says the wealthy and influential north-eastern region gets a raw funding deal from the central government and his centre-right Catalan Nationalist Coalition (CiU) will be hoping for a majority in the regional parliament.
His party argues a Catalan state would fare better as a member of the EU than a province of Spain.
The European flag has been prominent at his campaign rallies, and he says an independent Catalonia would quickly gain membership of the 27-member bloc.
The CiU ousted the Socialist party in elections in November 2010.
With 135 parliamentary seats available, Artur Mas knows that if he is to pursue his dream of an independent Catalonia, he will need a clear mandate from voters.
If not, Artur Mas will have to rely on the support of smaller pro-independence parties, our correspondent says.
Even then, the road to independence is far from straightforward.
A referendum would be illegal under the current Spanish constitution, and Spain’s ruling Popular Party is likely to block any attempts for constitutional change.
Other parties, such as the nationalist Ciutadans, the Popular Party of Catalonia the Socialist Party of Catalonia are all opposed to Catalonia’s independence bid.
The Catalan vote comes as the Basque separatist movement Eta indicates it is ready to disarm, disband and enter talks with the French and Spanish governments.
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