The two sides, who met during the group stage of the competition back in 2012-13, are both looking to reach the final for the first time.
Rafael Benitez's Napoli earned an impressive win over Wolfsburg in the last round to book their place in the semi-finals, triumphing 6-3 on aggregate.
Winning the Europa League could be their only passage into next season's Champions League following an indifferent few weeks in Serie A. The Neapolitans currently sit in fourth place in the table, four points adrift of the coveted top three positions and with four games left to play.
However, four victories from their previous six matches have boosted their hopes of securing a top-three finish. The team's last outing saw them overcome 10-man AC Milan 3-0 at the Stadio San Paolo.
Despite Napoli's strong run in the Europa League and a respectable domestic showing, Benitez's future at the club remains unclear. Amid rumours that he could return to England in the summer, president Aurelio De Laurentiis has admitted that he would like the Spaniard to continue at the helm.
Whether Benitez remains in charge of Napoli remains to be seen, but the 55-year-old has every chance of ending the season on a high with Champions League football and Europa League glory.
Recent form: WWWDWD
Recent form (all competitions): WWDWLW
Dnipro reached their first European semi-final last month when they knocked out Club Brugge to make it through to the last four of the Europa League.
Myron Markevych's side will travel to Italy full of confidence after losing just one of their previous 11 matches in all competitions. Out of those 11 games, eight have ended as wins for Dnipro.
On the domestic front, Dnipro currently sit in second place in the Ukrainian Premier League, six points behind Dynamo Kiev. They have not lost any of their last eight league games, while their most recent result saw them defeat Chornomorets 3-0 away.
While Dnipro have enjoyed an unprecedented run in this season's Europa League, their form away from home has been patchy. With three defeats, four draws and just one victory to their name, the visitors are expected to find life difficult against Napoli.
That said, having already defeated the likes of Brugge, Ajax and Olympiacos this season, Dnipro could well give themselves a solid platform on which to build during the second leg. Napoli will certainly be wary of their opponents because the away side are more than capable of springing an upset.
Recent form: WDWLDW
Recent form (all competitions): DWWWLW
Napoli have no fresh injury concerns heading into the match, though forward Michu remains sidelined with a thigh problem.
With bottom-placed Parma up next in the league this weekend, the hosts are unlikely to hold any players back for this match.
Napoli possible starting lineup:
Andujar; Maggio, Albiol, Britos, Ghoulam; Jorginho, Lopez, Callejon, Hamsik, Insigne; Higuain
Dnipro possible starting lineup:
Bokyo; Douglas, Luchkevych, Fedetskiy; Kankava, Leo Matos, Cheberyachko, Bezus, Rotan; Konoplyanka, Seleznyov
Head To Head
The teams' previous meetings came in the 2012-13 edition of the Europa League, with each beating the other during the group stage. Dnipro, who were managed by former Tottenham Hotspur boss Juande Ramos at the time, earned a 3-1 victory at home before Napoli recorded a 4-2 triumph in the return fixture.
We say: Napoli 2-0 Dnipro
While it is expected that there will be little to separate these two teams over two legs, home advantage could be vital for Napoli in the first encounter. The Italians have an impressive European record at the Stadio San Paolo, while Dnipro have been underwhelming on their travels this season. The Ukrainians are likely to adopt a dogged approach in an attempt to frustrate Napoli, but the hosts should gain the upper hand thanks to their quality going forward.