"Huge collision on Las Ramblas in Barcelona by an individual driving a van, many injuries," a statement from Catalan police said.
The area around the incident was cordoned off, with several ambulances and police vehicles on the scene, an AFP correspondent said.
Police in Barcelona, Spain's second-largest city, told crowds fleeing the scene by megaphone that they were dealing with a "terrorist attack".
The famous Las Ramblas boulevard is one of Barcelona's busiest streets, normally thronged with tourists and street performers until well into the night.
Spain has so far been spared the kind of extremist violence that has occurred in nearby France, Belgium and Germany.
Deadliest jihadist attack
But it was hit by what is still Europe's deadliest jihadist attack in March 2004, when bombs exploded on commuter trains in Madrid, killing 191 people in an attack claimed by Al Qaeda-inspired extremists.
Vehicles have been used in several terror attacks in Europe in recent years, including a jihadist massacre that claimed 86 lives in the French Riviera city of Nice.
That onslaught in July last year and other similar attacks were claimed by the Islamic State jihadist group.
In July 2015, a hooded attacker opened fire outside a hotel in downtown Barcelona near Las Ramblas, leaving two people injured, police said.
One person was struck by bullets while the other was hurt as they tried to flee the shooter, who fled the scene. No suspected motive for the attack was given.
Spain has emerged as a potential target for jihadists, with extremist websites mentioning it for historical reasons, since much of its territory was once under Muslim rule.
Generally, authorities in Spain -- the world's third largest tourism destination -- remain discreet on the terror threat.
But they publicise every arrest of alleged jihadists, most of them detained for propaganda, recruitment for extremist groups or "glorifying terrorism."
According to the interior ministry, more than 180 "jihadist terrorists" have been arrested since June 2015 when Spain raised the terror alert level to four out of a maximum of five, in domestic and foreign operations.