The Reds have not lost to non-league opposition in the FA Cup since 1959, when they were beaten by Worcester City, and only three times in their entire history.
And while a visit to the 7,574-capacity One Call Stadium, formerly Field Mill, will be viewed by many as a potential upset, Henderson thinks the squad will embrace the challenge.
"It'll be different to what we're used to in the Premier League," he said.
"But you always have different challenges in football. The players look forward to it, it's another opportunity for people to play.
"Everyone looks forward to playing football. People who haven't played may get an opportunity and it is an opportunity for them to stake a claim.
"We'll have to adapt to the situation. I'm sure all the players will have played at small stadiums like that before and it'll be a good atmosphere.
"We will have to go there with the right mentality and do a good job."
Henderson believes back-to-back league wins have wiped out memories of their dismal Boxing Day defeat at Stoke and ensured they head to Nottinghamshire buoyant.
"It'll be a tough game for us. It won't be a pushover," he added.
"It'll be the biggest game for many of those Mansfield players. They'll be really up for it, it'll be a cup final for them, so we have to treat it as a cup final and we do the job properly.
"We've won the last couple so we'll have good confidence going into the game.
"If we play like we are doing, then we can get a positive result."
Manager Brendan Rodgers is keen for his side not to under-estimate their opponents, even if he will rest the likes of top scorer Luis Suarez and captain Steven Gerrard.
"It's a tricky tie - that's why the cameras are there, hoping for an upset," said the Reds boss.
"They will be a team who are strong, organised and rely on set-pieces and their centre-half has an enormous throw.
"If you are a Mansfield player this is something you will never forget.
"It's real football. You get guys that are working hard at that level, in not always the best conditions.
"It's a final for Mansfield - you saw their faces after the Lincoln game when they qualified.
"For them to play against Liverpool, a club with such prestige, they're going to give their maximum."
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