The come-from-behind upset matched fellow fourth-tier amateur outfit Belfort’s shock defeat of Ligue 1 Montpellier on penalties 24 hours earlier.
Loic Remy put Lille into an early lead against the minnows who had ended Reunion islanders’ JS Saint-Pierroise’s dreams of becoming the first team from a French overseas territory to reach the last 16.
And they continued their adventure by hitting back hard in the second half with a double from Jean-Philippe Krasso.
“We were never in the match,” complained Lille coach Christophe Galtier.
“You have to congratulate Epinal who deserved this win. We didn’t deserve to get a lot out of the way we played.”
PSG ensured they did not get spellbound by the magic of the Cup at third division Pau.
Neymar stayed in Paris and Kylian Mbappe remained on the bench but the services of the world’s two most expensive footballers weren’t required as captain Leandro Paredes and Pablo Sarabia scored in either half for a drama-free 2-0 win.
“It wasn’t easy, it was our fifth consecutive away game,” said PSG coach Thomas Tuchel.
“We made a lot of changes but the lads did really well.”
PSG, beaten in last season’s final, have won the competition a record 12 times, two more than Marseille who also progressed by beating Strasbourg 3-1.
A group of around 600 Marseille lawyers dressed in courtroom robes demonstrated against the government’s pension reforms, brandishing banners before kick-off and after Bouna Sarr’s 32nd minute opener from the stands proclaiming “Marseille lawyers are going to win”.
And Marseille’s fans had a nervy wait before the final verdict of the Velodrome drama played out before them was certain.
Dimitri Payet’s penalty gave the hosts a healthy half-time lead but with Benjamin Corgnet putting Strasbourg back in business on 59 minutes Andre Villas-Boas’s side could only breathe easy after Boubacar Kamara’s goal deep in injury time.
On Tuesday Rennes, who had denied PSG a 13th title, took another step closer to retaining the trophy by edging a nine-goal thriller with top flight Angers 5-4.
Saint Etienne beat Monaco and Ligue 1 strugglers Dijon needed a 119th winner against plucky fifth division amateurs Limonest.
The last 16 concludes on Thursday with Lyon at Nice.
