The meetings between the two rivals are usually fiery encounters and the fixture is watched by millions across the world, with any decisions Atkinson makes set to be scrutinised in fine detail.
Riley stressed that it is important for Atkinson to have empathy for the nature of the fixture but to also make the right decisions.
Riley told Sky Sports: “The advice to the referee would be the same for that game as for the other 380 Premier League games – to use your skill set to referee it in a way that the league and the players expect.
“He will have to have an empathy and an understanding of the game but it’s also important to enjoy the occasion.
“In the Premier League you’re refereeing the best players in the world in the best stadiums in the world and you have to enjoy it.
“It’s a really delicate balancing act to having the empathy of the game and applying the laws and that’s what the skill of the referees have at this level.
“It’s one of the great things about refereeing at this level, that you’re doing hugely important games that are broadcast all around the world and the challenge of that is the fun part of the job.”
Atkinson has experience of overseeing high-profile games and was the referee for the recent fixture between Chelsea and Manchester City.
The 46-year-old has previously overseen three meetings between Liverpool and United, two of which were at Anfield.
So far this season Atkinson has shown eleven yellow cards and one red card across the four Premier League fixtures that he has been in charge of.
United go into the game in second place in the Premier League table, with Liverpool five places and seven points below them.