Los Blancos overcame Leganes in the round of 16 courtesy of a 3-1 aggregate score, while Girona shocked Atletico Madrid to make the final eight of the competition.
Real Madrid have won the Copa del Rey on 19 occasions but have not landed the trophy since 2014, with Barcelona utterly dominating the competition in recent years.
Los Blancos have actually only landed the Copa del Rey on two occasions since 1993, but it might well represent their best chance of silverware this season.
Madrid have booked their spot in the last-16 stage of the Champions League, but it is difficult to imagine the capital giants landing a fourth straight European title when considering the form they have shown this season.
Santiago Solari's side will enter this match off the back of a 2-0 win over Sevilla at the weekend, meanwhile, but they are still 10 points behind La Liga leaders Barcelona and it is very difficult to see the capital giants challenging for the title.
It has been a turbulent campaign for Real, who sacked Julen Lopetegui following a poor start. They are all but out of the title race due to Barcelona's current form, but the Copa del Rey does provide a genuine chance to land some domestic silverware, which has been hard for the club to find in recent years.
The current fixture list is not ideal when considering the club's injury problems, although players are just starting to return to the training field. Solari's side suffered a 1-0 defeat at Leganes in the second leg of their last-16 Copa del Rey clash last week, but managed to progress 3-1 on aggregate.
Real have three more domestic matches before the end of the month and will then open February with La Liga games against Alaves and Atletico Madrid before travelling to Ajax in the Champions League. It could yet be a successful campaign for the club, but it could also quite easily go the other way.
Recent form: WLWWWL
Recent form (all competitions): DLWWLW
The quarter-finals already represents Girona's best-ever showing in the Copa del Rey, and they will be looking to shock another of the Madrid giants to make the semi-finals of the competition.
Indeed, Eusebio Sacristan's side overcame Atletico in the round of 16 courtesy of a 3-3 draw at the Wanda Metropolitano in the second leg of their clash last week. Girona needed away goals to progress, with Seydou Doumbia's 88th-minute effort proving decisive.
Thursday will be just the fourth ever meeting between Real Madrid and Girona and indeed their first ever clash in the Copa del Rey. Girona recorded a 2-1 win in the first La Liga clash in October 2017, but have lost 6-3 and 4-1 to the Madrid giants in their last two encounters.
Girona finished 10th last season in their first La Liga campaign, while they currently occupy 12th position in Spain's top flight with 24 points from their 20 matches this term.
The Catalan outfit will enter the clash with Madrid off the back of a 3-2 defeat at Real Betis, however, and they have not actually picked up all three points in a La Liga clash since the end of November.
The Copa del Rey would not have been high on the club's list of priorities this season, but Girona are now on the cusp of the semi-finals and will have drawn plenty of confidence from their away-goals success over Atletico.
Madrid's form this season has been incredibly inconsistent, meanwhile, and a positive result in the first leg at the Bernabeu would leave Girona in with a strong chance of shocking the European champions.
Recent form: LDDWDD
Recent form (all competitions): DDDDDL
The trio returned to full contact training on Tuesday and could all be involved in the squad against Girona.
Vinicius Junior has been Real Madrid's standout attacker in recent matches, and the Brazilian will again start in the final third of the field.
Cristhian Stuani missed Girona's 3-2 defeat at Betis in La Liga at the weekend through suspension, but the experienced forward should return to the starting XI for this match.
Real Madrid possible starting lineup:
Courtois; Odriozola, Ramos, Nacho, Marcelo; Llorente, Kroos, Valverde; Vinicius, Benzema, Isco
Girona possible starting lineup:
Iraizoz; Ramalho, Espinosa, Muniesa; Porro, Granell, Luiz, Valery; Lozano, Garcia, Stuani
Head To Head
As mentioned, Thursday will be just the fourth ever meeting between Real Madrid and Girona.
Girona recorded a 2-1 win in the first La Liga clash in October 2017, but have lost 6-3 and 4-1 to the Madrid giants in their last two encounters.
It will be the first time that these two teams have locked horns in the Copa del Rey.
We say: Real Madrid 3-1 Girona
Girona's form in 2019 has not been great and we fancy Real Madrid to claim an advantage in the first leg, but it will not be straightforward for Solari's side.