Elsewhere on the card, it's a big night for Michael Smith as he attempts to break his duck against Gerwyn Price.
There's also a battle of the Scots as Gary Anderson looks to end his recent losing run against Peter Wright.
If that wasn't enough, the final quarter-final contest sees Jonny Clayton take on James Wade in a match with implications for both ends of the table.
Night three order of play
Michael Smith 19:10 Gerwyn Price
Joe Cullen 19:40 Michael van Gerwen
Gary Anderson 20:10 Peter Wright
James Wade 20:40 Jonny Clayton
Semi-finals will start at around 21:10 GMT, while the final is expected to take place at 22:15 GMT.
Michael Smith vs Gerwyn Price
The Premier League season is still in its infancy yet this already feels like an important week for Michael Smith.
Bully Boy is yet to win a game in the tournament having bowed out at the quarter-final stage in the first two weeks.
If that wasn't concerning enough, Smith has also struggled at the Players Championship having failed to get past the third round in any of the four events.
Gerwyn Price, in contrast, appears to be on the up. The Welshman reached a Premier League semi-final last week and followed that up with another semi-final run at Sunday's Players Championship - losing to Joe Cullen on both occasions.
Joe Cullen vs Michael van Gerwen
The second match on the card is arguably the most anticipated of the entire Premier League campaign so far.
Joe Cullen is the sport's in-form player after dominating the darting scene over the past month or so.
The man known as Rockstar followed up January's Masters win by reaching the Premier League final on night two and winning back-to-back Players Championship events in Wigan.
The 32-year-old is flying up the PDC's Order of Merit and arrives in Belfast having lost just three of his last 24 competitive games.
His opponent, Michael van Gerwen, has been far from his best for over a year now, but has shown glimpses of a potential return to form.
Mighty Mike reached the semi-final on night two of the Premier League, and averaged over 102 in both games.
The Dutchman had mixed fortunes at Players Championship events, but as we learned last week, you can never count out the three-time world champion.
Gary Anderson vs Peter Wright
An all-Scottish affair is third on the bill as Gary Anderson and current world champion Peter Wright go head-to-head for the third time this year.
The first meeting between the pair took place at the PDC World Darts Championships semi-final as Snakebite powered to a 6-4 victory in a high-quality contest.
A month later, the pair met in another semi-final - on this occasion it was the opening night of the Premier League season.
Wright enjoyed a blistering start and took a 5-2 lead as victory seemed inevitable. However, the Flying Scotsman rallied and won the next three legs to make it 5-5 and force a deciding one leg shootout.
In the end, Anderson failed to complete his comeback as Wright sealed a 6-5 victory.
Both men are coming into Thursday night in poor form having endured a disappointing weekend in the Players Championship and having failed to impress during last week's Premier League event in Liverpool.
With that in mind, there's a lot on the line when both these players step up onto the oche.
James Wade vs Jonny Clayton
The final quarter-final contest in Belfast sees league leader Jonny Clayton take on the man with the lowest tournament average, James Wade.
Clayton reached the final on the opening two nights of the Premier League - winning the last one 6-4 against Joe Cullen.
The Ferret has been one of the leading players on the PDC Tour for over a year and has won his last three games against Wade - including their Premier League semi-final clash two weeks ago.
Speaking of the Machine, the former Premier League winner is yet to impress in the competition.
Wade currently has the lowest tournament average at 89.36 - eight points down on Clayton.
The 38-year-old doesn't need to average three-figure sums to cause problems for his opponents. However, his current numbers are worrying and they could leave him lagging behind the rest of the field.
With that in mind, there's certainly a lot on the line in this one as Clayton looks to stay top of the table and Wade looks to drastically improve his average.
Who will go all the way?
There are two men who are worth keeping a close eye on this week - Joe Cullen and Jonny Clayton.
The Rockstar is enjoying the best darts of his entire career and will certainly take some beating in Belfast.
Clayton, meanwhile, is the current leader and is clearly loving life in the Premier League.
Considering their current form, don't be surprised to see a repeat of last week's final.