Kick-off is scheduled for 7 pm, with the Buccaneers aiming to secure a place in the quarter-finals as they turn their attention back to domestic competition following their successful CAF Champions League campaign.
Abdeslam Ouaddou's side booked their place in the continental tournament's group stages with a commanding 4-0 victory over African Stars on Friday, completing a 5-0 aggregate triumph.
The result represented a significant step forward after Pirates were eliminated by FC Saint-Eloi Lupopo of the Democratic Republic of Congo in the preliminary round last season.
However, Ouaddou expects his team to face a stern test against Milford, whom he regards as a well-coached outfit.
"The advantage, the positive point, is that we're playing at home, but I think it will be a difficult game. If you remember when we played Milford in the first game of the season, I said there are not many teams that will beat them," said Ouaddou.
"They have shown resilience, and they have shown a lot of confidence. They're a well-coached team, very disciplined, very organised. They can run as well, so it's not going to be an easy game."
The visitors arrive in encouraging form, having gone four matches without defeat. Their recent results include an emphatic 5-1 win over Richards Bay and a 1-0 victory against Golden Arrows in the Betway Premiership.
Pirates will also have one eye on Saturday's Soweto Derby against Kaizer Chiefs at a sold-out FNB Stadium.
Mamelodi Sundowns will look to put their CAF Champions League disappointment behind them when they host Marumo Gallants in the Carling Knockout last-16 clash at Loftus Versfeld Stadium on Saturday.
Kaizer Chiefs are looking to bounce back from their early CAF Confederation Cup exit when they battle TS Galaxy in the Carling Knockout Cup clash at FNB Stadium on Tuesday.
Orlando Pirates coach Abdeslam Ouaddou has provided a positive update on Oswin Appollis' recovery but insists the club will not rush the winger back into action despite his return to training.
AmaZulu coach Arthur Zwane has criticized his teams goal scoring performance after Last 16 Carling Knockout Cup 1-0 victory against Kruger United in Mbombela on Sunday.
