Two late strikes have helped Real establish a two-goal advantage ahead of the reverse fixture at Estadi Montilivi, but the underdogs do have two away goals to their name.
The Girona fairytale has hit somewhat of a blip over the past seven weeks with the team having failed to win in 10 matches in all competitions, but the end results do not tell the whole story.
A return of four points from their last eight league outings has left the club just three points adrift of the relegation zone, and there will be concern that further setbacks could lead to a battle to remain in La Liga.
However, overcoming Atletico Madrid in the last 16 of this competition was arguably an unprecedented high for Eusebio Sacristan's side and it proved that the first-team squad are capable of competing with the very best in Spain.
Having to face Real Betis, Real and Barcelona in the three games following that famous night at Wanda Metropolitano has not helped their cause, and having to take on another showdown with Real may be a step too far for this group of players.
Nevertheless, these are the games which Girona want to be involved in if they are to establish themselves in the top flight for years to come, and the hosts will be under no pressure when taking to the pitch on Thursday night.
Cristhian Stuani has only been used on one occasion in this competition during the current campaign, but Sacristan will surely call up his top goalscorer for this contest with the 32-year-old having contributed 12 goals in La Liga.
That said, Stuani was left on the bench when the teams met at Girona's home ground in August, with the hosts taking the lead and causing their more illustrious opponents plenty of problems until two penalties swung the match in the direction of Real.
That game was five months ago, but it has relevance heading into this week's contest and will provide Girona with the confidence that they can achieve their second successive Madrid scalp in the space of a couple of weeks.
Recent form: DWDDL
Recent form (all competitions): DDDLLL
Santiago Solari remains under pressure to keep his job at the Bernabeu, but the interim manager has at least got his side back on track at an important stage of the season when their campaign had threatened to unravel after the short winter break.
Three successive wins have been recorded in La Liga since the home defeat to Real Sociedad, while Solari's men are in a strong position to reach the last four of this competition.
Solari will take nothing for granted with Levante having threatened a comeback during the second leg of their last-16 tie, but Real arguably needed that game in order to remain switched on for the visit to Girona.
Victories over Sevilla, Girona and Espanyol have also produced 10 goals, and that is the kind of strike-rate that Solari will require in order to remain in charge past the end of the season.
The club are also on a high, having established themselves back in the top four of the La Liga standings after previously been heading towards mid-table at times under both Julen Lopetegui and Solari.
The next target is trying to overcome city rivals Atletico Madrid - who sit five points clear in second place - and their upcoming derby showdown would be staged just days after the first leg of the semi-finals.
Solari would be left with a selection headache with the league remaining the priority, but it is one which he will crave with Real looking to get their hands on the trophy for the first time since 2014.
The return of Gareth Bale is also a welcome boost for Solari, who will hope that the Welshman can build on the goal that he scored after coming off the bench at the weekend.
Recent form: WWWLW
Recent form (all competitions): WWLWWW
Bale was provided with 23 minutes as a replacement at the weekend, and Solari may look to hand a start to the forward for Thursday's match.
Bernardo Espinosa was also dismissed against Barcelona at the weekend, but the centre-back is free to feature against Real.
Borja Garcia has been suffering from a hamstring problem, but the creative midfielder should be fit enough to take his place in the squad.
Girona possible starting lineup:
Bounou; Alcala, Espinosa, Juanpe; Porro, A.Garcia, Pons, Granell, Fernandez; Stuani, Portu
Real Madrid possible starting lineup:
Navas; Carvajal, Varane, Nacho, Marcelo; Ceballos, Llorente, Modric; Isco, Bale, Junior
Head To Head
Girona have played Real on four occasions since their promotion to La Liga, and the minnows have scored in each of those outings.
A 2-1 win was recorded in front of their own supporters back in October 2017, but Real have netted a total of 14 times in the three games since that famous triumph.
We say: Girona 1-3 Real Madrid
Girona will believe that they still remain in this tie, but we cannot back against Real who we expect to deliver a professional performance and net the goals which will put the tie beyond their hosts.