Russian forces have targeted the industrial city and surrounding region persistently since their invasion two years ago.
"Four people were killed in the Russian attack on Dnipro this morning. Twenty seven people were wounded. Eleven of them have been hospitalised. Two are in serious condition," the regional governor Sergiy Lysak said on social media.
He had earlier described the attack as "vicious" and said a 14-year-old girl was among those wounded in the attack.
Amateur footage of the attack published by Ukrainian media showed a huge plume of black smoke rising over the city and drivers speeding from the scene.
The airforce said its air defence systems had downed six drones and five out of seven missiles that were mainly targeting Dnipro.
The head of the Dnipropetrovsk regional council described the barrage as "massive" and posted images showing buildings ripped open by the attack and shattered glass strewn across the ground.
"This is what one of the city's shopping centres looks like now. Cars and windows were smashed, and a petrol station was hit," Mykola Lukashuk said.
Dnipro had a pre-war population of around one million people and lies about 100 kilometres from the nearest point along the southern front line.
More than 40 people were killed in a Russian strike on Dnipro in January 2023, in one of the single-worst aerial bombardments by Russian forces.
Separately, officials in Ukraine's eastern regions of Donetsk and Kharkiv said two civilians had been killed in overnight Russian attacks.
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