The vehicle drove into crowds on Drottninggatan (Queen Street) - one of the city's major pedestrian streets, just before 3pm local time, before crashing into Åhlens Mall.
A number of people have been injured - Swedish police confirmed at least two people have been killed.
Stockholm police confirmed they are dealing with the incident - which is being treated as a suspected terror attack according to local media.
Armed police remain on the scene, and the area has been cordoned off.
The public has been warned to stay away from the city centre.
Stockholm’s Parliament has been evacuated and the area cordoned off.
Unconfirmed reports have emerged of a secondary incident - a shooting - in a separate area of the city. The public subway system has also now been stopped in the city.
Martin Svenningsen, a reporter with P4 Extra, says he saw a truck driving into the crowd.
He said: “I saw at least three dead, but there are probably more. It's a complete mess here.”
Several people are lying lifeless in the street according to witnesses, Expressen.se reported.
Towe Hägg of Stockholm police said: “We have have had the reports and have initial information about person injuries.”
Reports suggest the vehicle rammed through the crowded street drove into Åhlens Mall.
“I saw hundreds of people run, they ran for their lives,” Anna, who witness the incident said. “I turned and ran as well.”
Jan Granroth was inside a shoe store on Drottninggatan when he heard people starting to scream.
Peace & Love for your fellow man, the only philosophy that should be practiced. You cannot coexist with people who want to kill you.