France's interior minister Christophe Castaner told reporters at the scene "unfortunately the human toll is particularly serious."
He said two civilians and two firefighters had died of their injuries from the gas blast.
“As firemen were looking for a gas leak in the building, a dramatic explosion took place,” Castaner said, adding that one of the firemen had been buried under debris for several hours.
He said 10 people are in critical condition and 37 others less seriously injured.
He paid homage to the courage of rescuers who saved the life of one firefighter who was buried under the rubble for two and a half hours.
The accident occurred with Paris under security lockdown for a ninth consecutive Saturday of “yellow vest” protests, with large parts of the French capital blocked off by riot police.
As Castaner spoke, thousands of yellow vest protesters marched noisily but peacefully through the Grands Boulevards shopping district of northern Paris, just a few hundred metres (yards) from the location of the explosion.
In recent years, France has suffered a string of deadly Islamist militant attacks in Paris, Nice, Marseille and elsewhere but authorities quickly ruled out foul play.
“A this stage we can say it (the gas blast) is clearly an accident,” Paris prosecutor Remi Heitz told reporters.
A police source said the explosion tore apart a bakery on the rue Trevise and witnesses said the force of the blast shattered nearby storefronts and rocked buildings hundreds of metres away.
More than 200 firefighters joined the rescue operation and two helicopters landed on the nearby Place de l’Opera to evacuate victims. Ambulances struggled to access the blast area because of police barriers set up to help contain any violence by yellow vest protesters.
An eyewitness at a hotel nearby said he saw flames envelop the ground floor of the building blown out by the blast.
“There was broken glass everywhere, storefronts were blown out and windows were shattered up to the third and fourth floors,” said 38-year-old David Bangura.
He said that as he approached the scene, a woman was crying for help from the first floor of a building: “Help us, help us, we have a child”.
Paris Mayor Anne Hidalgo, who was also at the scene, extended a "message of affection and solidarity" to the victims.