Swansea are two places and three points above the drop zone ahead of the fixture, but with just one team in the bottom eight yet to play their midweek game, they have the chance to push themselves away from danger with a win.
The manager has seen enough in the performances in recent weeks to believe that they are capable of such a result too, despite the Gunners being the overwhelming favourites as they continue their title charge.
Speaking to the club's official website ahead of the fixture, Guidolin referred back to a previous encounter between him and Arsenal in 2011, when he was in charge of Udinese.
The two teams faced each other in a Champions League play-off ahead of the 2011-12 campaign - a play-off the Gunners won 3-1 on aggregate, having won 1-0 on their own patch and 2-1 in Italy.
However, the games were very close, with Guidolin saying that he "remember[s] two balanced, difficult matches for both teams."
Having been pleased with the way his team played in those two games five years ago, the Italian now "hope[s]" to see his new side, Swansea, "play well" at the Emirates tonight.
Not only is the manager familiar with the team he is facing later on, but a particular player too in Alexis Sanchez. The Chilean spent five years with Udinese between 2006 and 2011, leaving for Barcelona just a month before the double-header with Arsenal having spent a season under Guidolin's charge.
The Swansea boss picked out Alexis as an "important" player for a "good team" who will give his side "a difficult match," adding that he is "happy" for the forward given the success he has enjoyed in his career since moving on from Serie A.
However, whilst Guidolin says he "hope[s]" to be able to "have [Alexis'] shirt after the game," he also hopes "to have the points" for Swansea.
Guidolin confident of survival
Swansea come into this game off the back of a good performance elsewhere in North London at the weekend, albeit off the back of another defeat having lost 2-1 to Arsenal's bitter rivals, Tottenham Hotspur.
Whilst it was not a 'must-win' game for the Swans, with them facing an in-form opponent who are in the title race, it was disappointing for them to once again take the lead in a match and surrender it - the third time in their last four games that they have done so.
The defeat leaves Swansea still well involved in the relegation battle, which Guidolin cited as "a problem" and something that leaves them "a little bit worried."
"This season is not easy," said the Italian, "but my opinion is that we have the possibility to play well in the last part of the season" - something he is "confident" about.
Since arriving, Guidolin says he has "seen [his] team play well in many games," which gives him belief that the campaign can be ended on a high.
"We have to survive this season," he stressed, saying that this is the "target" and they will look to achieve it by "think[ing] match by match."
“We know we have a battle for three months but I am positive.”