Top-seeded Stan Wawrinka, ranked No. 9, went down 6-7 (5), 6-4, 6-4 to 74th-ranked Federico Delbonis of Argentina.
The 2014 Australian Open champion extended an unwanted record of never having won a tour title in his native Switzerland.
In the semifinals, Delbonis will play sixth-seeded Joao Sousa of Portugal, who rallied to a stunning victory against Pablo Andujar of Spain 6-4, 2-6, 7-6 (6).
Sousa faced four match points trailing 6-2 in the decisive tiebreaker then reeled off six straight points to take victory.
Second-seeded Cilic was beaten 7-5, 6-3 by Santiago Giraldo of Colombia.
Cilic, who has been troubled by a shoulder injury this year, has advanced to only one tournament semifinal since winning the U.S. Open title last September.
The 10th-ranked Croatian had nine aces on the clay-court surface but failed to create a break-point chance against the 67th-ranked Giraldo.
Giraldo will play Thomaz Bellucci of Brazil in an all-unseeded semifinal.
Bellucci, a two-time champion at the neighboring Swiss Open in Gstaad, beat Albert Ramos-Vinalos of Spain 6-0, 1-6, 6-3.