The visitors were well beaten by Christophe Galtier's men, who are now only three points behind Lille in the race for the final UEFA Champions League spot.
Defeat keeps the 2010-11 Ligue 1 champions seven points behind leaders Paris Saint-Germain and two adrift of second-placed Monaco, who both play on Sunday against Nantes and Toulouse respectively.
Brandao opened the scoring 10 minutes into the second half, the Brazilian striker netting only his second league goal of the campaign.
The former Marseille man was presented with the simple task of nodding home at the far post from Faouzi Ghoulam's excellent left-wing cross.
And Saint-Etienne's advantage was doubled six minutes later through midfielder Franck Tabanou, who reacted quickest to fire home on the half-volley after Romain Hamouma's initial shot had been well saved by Vincent Enyeama.
Lille were reduced to 10 men in the immediate aftermath of the goal as their miserable night was capped off when midfielder Florent Balmont was dismissed by referee Benoit Bastien for dissent.
