The Ospreys lie in fourth going into the game while the Blues and Scarlets are fifth and sixth respectively, just five points behind.
"In the context of the season, as it is now, then possibly it is (the biggest Welsh derby in the history of the Magners League)," said Holley.
"We have had some big, big derby games against the Blues at the Millennium Stadium and clearly the Scarlets derby for us is a massive game for us every Christmas, but in the context of this season it's a pretty big one, it's up there.
"There is a lot at stake in this one now. Clearly the Magners play-offs is the thing that is at the front of everybody's mind."
"There is always so much at stake with these games.
"It's probably seen as a must-win game for both teams. With the Blues losing at home last week to Munster it's probably a game they feel they have to win.
"Likewise, we lost up in Edinburgh and we want to put that right straight away, so it's a massive game. I just hope there is going to be a good turn out for it and it's a great occasion."