Gastao Elias upset Juan Martin del Potro to book an Open Parc Auvergne-Rhone-Alpes Lyon quarter-final clash with top seed Milos Raonic.
The Portguese, ranked 125th in the world, downed sixth seed Del Potro 7-6 (7-0) 6-4, while Raonic was also a straight-sets winner, defeating Denis Istomin 6-4 6-3 in France.
Jo-Wilfried Tsonga needed three sets to see off Carlos Berlocq, the second seed eventually winning through 6-7 (2-7) 6-2 6-3.
He will meet Karen Khachanov following the Russian's 6-2 7-6 (7-3) triumph over Jordan Thompson.
Also on Wednesday, third seed Tomas Berdych defeated Chung Hyeon 6-3 7-5 to book a last-eight match with Gilles Simon.
The Frenchman was a 3-6 7-5 6-4 victor against Kyle Edmund.