Simon got by Bernard Tomin 7-6 (10-8), 6-3 in a relatively quick 71 minutes. Simon lost his serve once but made up for it by taking the lengthy first-set tiebreaker. He had the only break of the second set.
Seppi, who won this tournament in 2011 and was the runner-up in 2012, defeated Radek Stepanek 6-4, 6-2 with a pair of breaks in each set.
Simon and Seppi will square off in the second semifinal Friday after Ivan Dodig and Feliciano Lopez decide who will be the first to reach the final.
Dodig made the semifinals with a 6-3, 6-2 upset of eighth-seeded Fabio Fognini in a brisk 56 minutes. Dodig had 10 aces and lost just 11 points over his nine games serving.
Lopez was a 6-4, 7-6 (8-6) winner over Spanish countryman Fernando Verdasco. Lopez lost 14 points in 11 games serving.
'How to Train Your Dragon 2' releases 5-minute clip
Moore to attend retreat in to avoid Kutcher's wedding