Wales have failed to beat any of the southern hemisphere's big three in the last 22 attempts and have only won one in 27 games since Warren Gatland took over as coach in January 2008. Their only victory came six years ago against Australia and following defeats against the Wallabies and All Blacks this month, they are desperate to beat South Africa.
Wales were unlucky to lose 31-30 to the Springboks in Nelspruit earlier this year, while they also came close to beating the Wallabies a few weeks ago, losing 33-28. During last week's match against the All Blacks in Cardiff, Wales led 16-15 late in the game, before the All Blacks ran riot with three tries in the last ten minutes to win 34-16.
But they face a somewhat depleted South African side on Saturday, as the Boks are without a few of their overseas-based stars.
Mitchell, via a column on the ESPNscrum website, said now is the best time for Wales to finally break their duck against on of the southern hemisphere giants.
He wrote: "Wales will be desperate for a Springbok scalp on Saturday and won't have a better opportunity to beat South Africa, who are without their overseas-based players.
"If Wales beat an understrength Springbok team on Saturday, Gatland will need to be very careful how he communicates the outcome to his players and stakeholders alike. He can't afford for them to get too carried away.
"In saying that, beating a top southern hemisphere side, at last, and breaking through that mental barrier, would do wonders for Wales' confidence heading into a World Cup year."
The Springboks and Wales have faced each other on 29 occasions, with the Boks winning 27 of those. Wales' only victory came in Cardiff in 1999, while there was also a draw in 1970.
Kick-off for Saturday's clash at the Millennium Stadium is scheduled for 16:30 (SA time).
Teams:
Wales:
15 Leigh Halfpenny, 14 Alex Cuthbert, 13 Jonathan Davies, 12 Jamie Roberts, 11 Liam Williams, 10 Dan Biggar, 9 Rhys Webb, 8 Taulupe Faletau, 7 Sam Warburton (captain), 6 Dan Lydiate, 5 Alun Wyn Jones, 4 Jake Ball, 3 Samson Lee, 2 Scott Baldwin, 1 Gethin Jenkins
Substitutes: 16 Emyr Phillips, 17 Aaron Jarvis, 18 Rhodri Jones, 19 Luke Charteris, 20 James King, 21 Mike Phillips, 22 Rhys Priestland, 23 Scott Williams
South Africa:
15 Willie le Roux, 14 Cornal Hendricks, 13 Jan Serfontein, 12 Jean de Villiers (captain), 11 Lwazi Mvovo, 10 Pat Lambie, 9 Cobus Reinach, 8 Duane Vermeulen, 7 Teboho “Oupa” Mohoje, 6 Marcell Coetzee, 5 Victor Matfield, 4 Eben Etzebeth, 3 Coenie Oosthuizen, 2 Bismarck du Plessis, 1 Tendai Mtawarira
Substitutes: 16 Adriaan Strauss, 17 Trevor Nyakane, 18 Julian Redelinghuys, 19 Lood de Jager, 20 Nizaam Carr, 21 Francois Hougaard, 22 Handré Pollard, 23 Damian de Allende
In his column, Mitchell also lauded New Zealand-born Joe Schmidt for the work he has been doing as Ireland coach.
CLICK HERE to read Mitchell's full column on ESPNscrum.