Former Arsenal captain Alexandre Lacazette led Lyon to the last 16 of the French Cup with a hat-trick against fifth-tier team Chambery.
All of Lacazette’s goals were scored from close range after receiving cutbacks.
Lyon, coached by Laurent Blanc, last won the competition in 2012 and currently sit in ninth place in Ligue 1.
Defending champions Nantes will face fifth-tier club ES Thaon on Sunday at 17:30 GMT.
On Monday, Ligue 1 leaders Paris St-Germain will aim to prevent an upset against sixth-tier team Pays de Cassel.