S-300 missiles hit the town of Pokrovsk in Ukrainian-held territory in Donetsk region, the regional governor said.
“The enemy is cynically hitting civilians, trying to bring as much misery as possible,” Governor Vadim Filashkin posted on Telegram.
In his evening video address, President Volodymyr Zelensky said Russian forces had targeted residential areas.
Russia should always feel consequences for such attacks, Mr Zelensky added.
Russia is yet to comment.
Pokrovsk is about 70km (43 miles) north-west of Donetsk city, which is occupied by Russian forces.
Before the war it had a population of about 60,000 people. Some residents have been returning despite official warnings about the dangers.
In August, at least nine people were killed and dozens more injured in a Russian missile attack on the town.
Earlier this week Ukrainian forces launched more than 70 drones across the border into Russia after Moscow launched its biggest aerial bombardment. This led to evacuations in the south-western city of Belgorod.
