Jackson Martinez will lead the line for the hosts, while compatriot Carlos Bacca will be looking to fire the Rojiblancos to an away winPorto and Sevilla will both hope to bounce back from domestic defeats when they clash in the Europa League on Thursday.
Nacional edged out Porto 2-1 in the Primeira Liga on Saturday but the latter's boss, Luis Castro, should be confident of a better performance when his team host Sevilla in their quarter-final first leg, as the 52-year-old coach rested several players on the local front.
Portuguese winger Silvestre Varela and French defender Eliaquim Mangala were the first-team regulars left out of the squad completely against Nacional, after both played in Porto's 1-0 Taca de Portugal victory over Benfica last week.
Both Varela and Mangala have started all four of Porto's Europa League matches so far this season after the Portuguese club dropped into the competition from the Champions League group stage.
Castro, who replaced Paulo Fonseca as Porto coach at the start of March, may also be tempted to bring in the likes of Josue and Carlos Eduardo, if he wants to further freshen up Porto's line-up, with the attacking midfield duo on the bench against Nacional.
Sevilla coach Unai Emery will not be able to blame his team's 1-0 defeat at Celta Vigo on an experimental side.
Instead, Emery should simply remind his team that they are in form, having won eight of their last 10 matches in all competitions.
Ivan Rakitic is Sevilla's main man with the Croatian attacking midfielder having scored 16 goals in all competitions this season, while he also has 18 assists.
The 26-year-old's brilliant control and pass to set up Carlos Bacca's second goal in Sevilla's 2-1 win over Real Madrid a week ago underlined his quality.
With Bacca banging in the goals for Sevilla, having scored 19 in all competitions, Thursday's game will pit two of Colombia's leading strikers - behind Radamel Falcao - against each other, with Porto's Jackson Martinez having notched 21 goals this season.
Sevilla reached the quarter-finals of the Europa League with a shootout victory over local rivals Real Betis after their two-legged round-of-16 tie ended 2-2 on aggregate.
Porto defeated Napoli 3-2 on aggregate after claiming a 2-2 draw in Italy.
It has been a frustrating season for the reigning Primeira Liga champions, with Porto's loss to fifth-placed Nacional seeing Castro's team sitting in third in the table, 15 points adrift of leaders Benfica.
Sevilla are flying in Spain despite their loss to 11th-placed Celta, with Emery's side in fifth and battling for consecutive Europa League qualifications.