Xavi's men have overcome two lower-league outfits in Barbastro and Unionistas to make it this far, sinking the former 3-2 before battling to a 3-1 away win over the latter team earlier this month.
Victory over Athletic would mark a third win in a row for Barca across all tournaments, as thanks in no small part to a Ferran Torres hat-trick, the Blaugrana beat Real Betis 4-2 in La Liga action over the weekend.
Here, Sports Mole rounds up Barcelona's latest injury and suspension news ahead of their clash with Athletic, whose last-32 clash with Eibar ended in a routine 3-0 triumph.
Marc-Andre ter Stegen
Status: Out
Type of injury: Back
Possible return date: Unknown
Marc-Andre ter Stegen is on the mend after undergoing back surgery in November, and the German goalkeeper is still facing another few weeks on the sidelines.
Gavi
Status: Out
Type of injury: Knee
Possible return date: Unknown
Ter Stegen was not the only November international casualty for Barcelona, whose former Kopa Trophy winner Gavi sustained an ACL injury while playing for Spain, and he is not expected to feature again this season.
Marcos Alonso
Status: Out
Type of injury: Back
Possible return date: Unknown
Marcos Alonso joins Ter Stegen on the back injuries list, having also been forced to go under the knife to treat a similar problem, and the left-back is expected to return to action at some point in the spring.
Inigo Martinez
Status: Out
Type of injury: Muscle
Possible return date: Unknown
Inigo Martinez, whose fledgling Barcelona career has been plagued by fitness concerns, aggravated a previous hamstring issue against Barbastro and will be absent for at least another couple of weeks.
Andreas Christensen
Status: Minor doubt
Type of injury: Ankle
Possible return date: January 24 (vs. Athletic)
Andreas Christensen only lasted until half time in the 3-1 beating of Unionistas due to discomfort in his ankles, but subsequent assessments have ruled out a significant injury, and he could be back in action on Wednesday.
Joao Cancelo
Status: Major doubt
Type of injury: Knee
Possible return date: January 24 (vs. Athletic Bilbao)
On-loan Manchester City defender Joao Cancelo missed Barcelona's unsuccessful Supercopa de Espana campaign and their meetings with Unionistas and Betis due to a knee strain, but he is believed to be in with a chance of making the squad in midweek.
Raphinha
Status: Out
Type of injury: Thigh
Possible return date: January 31 (vs. Osasuna)
Raphinha's Super Cup campaign ended prematurely as he sustained a thigh injury in Barca's semi-final beating of Osasuna, although he could potentially make his return against the same opponents later this month.
BARCELONA'S SUSPENSION LIST
Barcelona have no players suspended for this match.