The Reds must win by a 1-0 scoreline or by two goals or more in their final Group C encounter, or face a premature exit from the Champions League just seven months on from their final defeat to Real Madrid.
Klopp's men were beaten 2-1 last time out at the Parc Des Princes by Paris Saint-Germain, who travel to Serbia to face Red Star Belgrade also needing a win to be sure of qualification to the next round.
Napoli are in pole position at the top of the group and head into Tuesday night's clash against Liverpool needing only a point to progress, but Klopp insists his players cannot be inhibited by any fear of conceding a goal.
"You don't have a situation like this 20 times in your career," he told Sky Sports. "That's why I think it makes sense that our approach before a game will be completely normal,
"We don't want to concede always, that's how it is, and we want to win, that is also how it is. The rest we will see during the game.
"We need to be really active, very focused, very in the game but it's not that we are afraid of conceding goals before the game starts.
"They (Napoli) should have to work very hard for any chance and then we still have the opportunity to save it. And on the other side, we have to score.
"The only thing that is clear is if we go 1-0 up then it is not like it would usually be at 1-0.
"If they score we then have to score a second and a third and that is a very hard job to do. We knew that already. Now we have to do the job."
Liverpool are currently top of the Premier League and have only conceded six goals in their first 16 matches of the 2018-19 campaign - which is the best defensive record in England.
However, the Reds have already conceded one more goal than that in their first five European fixtures, with three away defeats to their name in Group C.
At Anfield, they have managed to pick up maximum points though and Klopp is hopeful his team can rise to the occasion once again.
"We were all not 500 times in a situation where 1-0 is good but 2-1 is not, 3-1 is good again but 3-2 is not," he added.
"It is a mix of being really lively, and making an emotional game of it - it must be - and on the other side being really closed at the back so nothing happens there.
"That is a big job to do but the boys have played many times and pretty good as well. We know how to be solid and be active."