Simon, who won the event in 2007 and '08, got past Lukasz Kubot 3-6, 6-1, 6-3. Simon dropped his serve once in each set but had three breaks each in the second and third sets.
Fabio Fognini outlasted sixth-seeded Andreas Seppi for a 6-4, 6-7 (4-7), 6-4 win in a match that took more than 3 hours. Fognini forced Seppi into 17 break-point situations and was able to finish off eight of them, including four in the third set.
Seppi's loss left Simon as the only seeded player to make the semifinals.
In other matches, Matthias Bachinger stopped Daniel Brands 6-4, 6-1 and qualifier Attila Balazs posted a 4-6, 6-3, 6-4 decision over Xavier Malisse.
Simon will take on Bachinger in the Saturday semifinals and Fognini goes against Balazs. Simon beat Bachinger earlier this year in their only previous meeting. Fognini and Balazs will meet for the first time in tournament play.
Swim Week Miami Beach 2014 [PHOTOS]