Free State Stars will host provincial rivals Bloemfontein Celtic in the first semifinal, while SuperSport United entertain Tshwane rivals Mamelodi Sundowns.
It is the first time that any of these sides have met in the Telkom Knockout competition and ensures there will be one team from each centre in the December 1 final.
The Tshwane match is a repeat of the Nedbank Cup final played earlier this year when SuperSport triumphed 2-0 over Sundowns to lift the trophy.
Matsatsantsa will in fact be aiming for a third successive cup final, having also lost the MTN8 decider to Moroka Swallows earlier this season.
Celtic and Stars have made rare visits to the final of this competition, with the latter yet to lift this trophy, and the former were winners in 1994.
Both matches are likely to be keenly contested and it is difficult to pick a clear winner from either.
The games will be played on the weekend of November 17/18, with the PSL Cup Committee to decide the exact dates, kick-off times and venues later this week.