Simon, 20th in the world, topped fifth-seeded Tomas Berdych and Janowicz, No. 69 in the rankings, was up 3-6, 6-1, 4-1 when eighth-seeded Janko Tipsarevic retired.
As a result, only one seeded player -- No. 4 David Ferrer -- will make the tournament semifinals. That is remarkable in a Masters series that has been dominated by the highest-ranked players.
Ferrer defeated sixth-seeded Jo-Wilfried Tsonga 6-2, 7-5 in his quarterfinal without facing a break point. Ferrer dropped just 15 points over 10 games serving.
His semifinal opponent will be No. 121-ranked Michael Llodra, who finished off the day's schedule with a home crowd-pleasing 7-6 (7-4), 6-3 decision over Sam Querrey. Llodra saved all five break points he faced and pounded out 13 aces against just one double fault.
This duo had wrecked the seedings, taking out four seeded players before meeting Friday. Llodra topped 10th-seeded John Isner and seventh-seeded Juan Martin del Potro. Querrey ousted second-seeded Novak Djokovic and No. 14 Milos Raonic.
Not to be outdone, in addition to Tipsarevic, Janowicz earlier beat world No. 3 Andy Murray and 13th-seeded Marin Cilic. Against Tipsarevic, Janowicz dropped serve just once and didn't face a break point over the last two sets while converting half of his eight break chances.
Simon fought off nine of 10 break points against Berdych and managed three breaks to advance.
Saturday's semifinals will be the first meeting between Simon and Janowicz. Ferrer is 2-0 in his matches with Llodra.
Swim Week Miami Beach 2014 [PHOTOS]