MacDonald was not picked in the original Highlanders squad but got his chance because of the dreadful run of injuries the Highlanders have sustained this year.
The experienced lock took his chance when he came on in the second spell against the Bulls last weekend.
In the first spell, the Highlanders were outplayed by the classy Bulls pack and lock Juandre Kruger played a dominating role. The Bulls made four takes off Highlanders throws.
"Hoani came on after halftime and settled down our lineout," coach Jamie Joseph said. "The lineout was an area of concern for us last week.
"Having a couple of lineout specialists in our team this week gives us the confidence that we can execute properly."
Incumbent Josh Bekhuis, who has been part of the locking pair in every game this season, pulled a groin muscle and did not train in the early part of the week. He moves to the bench.
MacDonald is one of five changes Joseph has made to the team that started against the Bulls last weekend.
The other change to the forward pack sees the return of All Black hooker Andrew Hore to the front row.
Hore also played a role in the Highlanders' lineout improvement with his accurate throwing in the second spell.
Jason Rutledge, who was guilty of loose throws, will sit on the bench.
MacDonald replaces Nick Crosswell, who moves to No 8 to replace Nasi Manu, who has an ankle injury.
Openside flanker Tim Boys, another player brought into the squad because of injuries, retains his starting spot.
He is the first genuine speedy No 7 the Highlanders have had since John Hardie was injured.
"Tim had an outstanding game against the Bulls," Joseph said.
"He tackled like a demon, put pressure on Morne Steyn, and was everywhere on the field.
"He went from the mai mai in Invercargill to one of the biggest games of his career last week against the Bulls. It was also one of the biggest games of the season for us as a team.
"The challenge for Boysie is to front up again. All his team-mates have been playing that sort of rugby every week," Joseph said.
"If he can play anywhere close to what he did last weekend he'll have another fine game and that's what we are after."
In the backs, old hand Jimmy Cowan starts at halfback instead of Aaron Smith, and will link with Chris Noakes, who replaces Mike Delany at first five-eighth.
Kurt Baker also comes into the starting XV to replace right winger Siale Piutau, who drops out of the 22 due to a thigh injury.
The match takes on additional significance as the Gordon Hunter Memorial Trophy is at stake.
The Highlanders regained it with their 30-27 win in Dunedin earlier this season.
The Highlanders need to win to keep their playoff hopes alive, while the Blues will be desperate for a win to give some credibility to their season.
The Highlanders are just outside the top six, only two points behind the sixth-placed Sharks on the table.
Their last three games are against the Crusaders, Chiefs and Reds and none of them will be easy.
"If we win we will have a better chance of making the playoffs," Joseph said.
"We come up against a hurting Blues team and that poses a difficult game for us.
"We've had our senior players away at the All Blacks camp at the start of the week and that means this week is equally as difficult as last week."
Blues coach Pat Lam has talked about wanting to bounce back from the embarrassment of last weekend's 59-12 loss against the Crusaders.
But he has named three of his All Blacks on the reserves bench in a move that will make the task against the Highlanders that much harder.
Ali Williams, in his 100th Super rugby game, Ma'a Nonu and Piri Weepu have been benched following the national team's training camp in Auckland. Only prop Tony Woodcock has been named to start.
Keven Mealamu and Charlie Faumuina, the other Blues involved with the All Blacks, are unavailable due to calf injuries.
There are 13 changes to the last Blues squad that met the Highlanders.
