Los Che have beaten two lower-league teams to reach this stage, while the Lions battled their way past three sides from outside the top flight before beating Espanyol in the previous round.
Match preview
Valencia have experienced mixed fortunes since the turn of the year, winning two, losing two and drawing one of their five matches across all competitions.
Los Che secured a comfortable 4-0 away victory against Sporting Gijon in the last 16 of the Copa del Rey last week, before being held to a 2-2 draw at home against Almeria in La Liga on Monday.
A run of just one win in their last nine top-flight matches has seen Valencia slip to 12th in the table, sitting just three points clear of the relegation zone, and Gennaro Gattuso will now be hoping his side can make the most out of their Copa del Rey campaign in a bid to rebuild a positive run of form.
Valencia enjoyed a successful cup run in the competition last season, beating Bilbao 2-1 over two legs in the semi-finals before losing out on penalties in the final against Real Betis, ending their hopes of replicating the triumphant feat of 2018-19.
Los Che head into Thursday's contest having won only one of their last eight meetings with Bilbao across all competitions, so Gattuso's side will need to be on top of their game if they wish to progress to the last four.
Like Valencia, Athletic Bilbao have also won two, lost two and drawn one of their opening five matches this year, with their most recent fixture ending in defeat against La Liga holders Real Madrid on Sunday.
Goals from Karim Benzema and Toni Kroos condemned the Lions to their sixth league defeat of the season and Ernesto Valverde's side remain eighth in the table, five points behind the Champions League positions.
Bilbao now turn their focus to the Copa de Rey, a competition they have won 23 times in total - four more than Real Madrid - with their last triumph dating back to the 1983-84 season under the tutelage of club legend Javier Clemente.
The Basque-based outfit, who beat Espanyol 1-0 in the last 16 earlier this month, have fallen short in the Copa de Rey in each of the last three seasons, losing in the final against Barcelona in 2019-20 and Real Sociedad in 2020-21 before suffering defeat in the semi-finals to Valencia in April last year.
Bilbao managed to gain revenge over Valencia when the two sides locked horns in La Liga earlier this season, securing a slender 1-0 home win in August, and Valverde's men will attempt to frustrate Los Che again on Thursday as they bid to reach the Copa del Rey semi-finals for the fourth successive year.
Valencia Copa del Rey form:
W
W
Valencia form (all competitions):
L
W
L
L
W
D
Athletic Bilbao Copa del Rey form:
W
W
W
Athletic Bilbao form (all competitions):
D
W
D
L
W
L
Team News
Valencia duo Nico Gonzalez and Jaume Domenech are both ruled out with respective foot and knee injuries, while Thierry Correia is doubtful with a muscle problem.
After watching on as an unused substitute last time out, centre-back Mouctar Diakhaby could be recalled to the first XI at the expense of Cenk Ozkacar.
Top scorer Edinson Cavani, who netted a brace in the previous round against Sporting Gijon, is set to lead the line and could be supported in attack by Samuel Lino and Justin Kluivert.
As for Bilbao, central defender Inigo Martinez is ruled out with a foot injury, but Yeray Alvarez is available after serving a suspension and will likely start at the heart of the defence alongside Dani Vivian.
Valverde is unlikely to make too many other changes to his starting lineup, with either Dani Garcia or Ander Herrera potentially replacing Oier Zarraga in centre-midfield, while striker Gorka Guruzeta will be hoping to force his way back into the side.
Valencia possible starting lineup:
Mamardashvili; Foulquier, Paulista, Diakhaby, Gaya; Musah, Guillamon, Almeida; Kluivert, Cavani, Lino
Athletic Bilbao possible starting lineup:
Simon; De Marcos, Alvarez, Vivian, Yuri; D. Garcia, Vesga; I. Williams, Sancet, N. Williams; Guruzeta
We say: Valencia 0-1 Athletic Bilbao
A low-scoring closely-fought contest is to be expected on Thursday, considering no more than two goals have found the net in any of the last six meetings.