Alan Dickens believes the big stage can bring the best out of Saints on Saturday.
Harlequins will provide the opposition in Big Game 10, which is set to be played in front of more than 70,000 fans at Twickenham.
Saints go into the match on the back of 12 defeats from their past 13 games in all competitions, including six successive Aviva Premiership losses.
But Dickens feels the final game of 2017 can help his team turn the tide.
"It's always a good ground to go and play at," said the interim head coach.
"It's an experience we've gone through (when Saints beat Harlequins 30-25 at Twickenham) in 2014 and it's a great occasion.
"Not only is it at Twickenham, but it's the first game on terrestrial TV.
"I'm sure it's a game the boys will relish being involved in."
Harlequins have also endured some tough times of late, losing five of their past six matches in all competition.
They currently sit ninth in the Premiership standings, one place and three points above Saints.
And Dickens, who gave his players Christmas Eve, Christmas Day and Boxing Day off, said: "They've shown glimpses of really good performances, like when they beat Saracens at home.
"They're a team similar to us in terms of the fact they're probably frustrated in how they've performed.
"We need to go to Twickenham, put in a performance and get the result we've worked so hard for."