Lukaku looked like the dynamic target man Everton fans have been hoping to see all season and could have scored five in a rampant display in the first leg of their last-32 clash in Switzerland.
His perfect treble of right-footed, left-footed and headed goals were among the highlights of a superb end-to-end encounter, that was perhaps only pipped for sheer entertainment by the game at Celtic Park where five of the six goals came in a dramatic opening 45 minutes.
Inter let slip a two-goal lead and then a 3-2 advantage as Celtic levelled in the third minute of stoppage time in a duel between two former European champions.
Napoli were among the other first-leg winners, beating Trabzonspor 4-0 away, and were considerably happier than Serie A rivals AS Roma whose status among the favourites looked questionable after a disappointing 1-1 home draw with Feyenoord.
While Gervinho opened the scoring for Roma with a deft flick from close range, Colin Kazım Richards netted a simple chance to level the scores with a potentially precious away goal.
Liverpool, one of the eight teams to have dropped into the Europa League from the Champions League, needed a late penalty from Mario Balotelli to take a 1-0 first-leg advantage against Turkish side Besiktas.
But typically with Balotelli, the finale was not without controversy as the Italian striker wrestled the ball off designated penalty taker and captain for the night Jordan Henderson, before firing home.
QUITE UNIQUE
It was Lukaku, who proved the star of the night, however, becoming only the fourth Everton player to score a European hat-trick.
"I've always said Rom is quite unique because you don't get many players with that pace and power," Everton boss Roberto Martinez said on the club website.
“He is a great target in our build-up play, but then in the same manner when the game was stretched tonight, his penetration, his desire to get on the end of things and then three clinical finishes was huge for us."
Young Boys grabbed an early opener with a superb curled effort from Guillaume Hoarau whose delight was swiftly crushed as Everton netted four times before Hoarau horribly fluffed a penalty in the second half.
Not even the sending-off of Everton defender John Stones, which brought about that penalty, could upset the visitors' rhythm as Martinez's side continued to prove a much more fearsome prospect in Europe than in the Premier League.
Celtic famously became the first British team to be crowned European champions when they beat Inter in 1967 but the Scottish champions looked to be heading to a fifth straight defeat against Italian opposition when Xherdan Shaqiri and Rodrigo Palacio put Inter 2-0 up after 13 minutes.
Two goals in two minutes from Stuart Armstrong and an own goal from Hugo Campagnaro levelled before Palacio's second put Inter back in front with a fifth goal before halftime.
That's how it stayed until the clock ticked past 90 minutes and Celtic's on-loan striker John Guidetti fired into the roof of the net chasing down Liam Henderson's pass to leave the tie all square heading into next week's second leg.
Sevilla stayed on course to retain their title with a 1-0 home win over Borussia Moenchengladbach while Tottenham Hotspur drew 1-1 at home to Fiorentina.
Elsewhere, Zenit St Petersburg were 1-0 winners at former European champions PSV Eindhoven, Bundesliga side VfL Wolfsburg won 2-0 at home to Portuguese team Sporting and Torino drew 2-2 with Athletic Bilbao.
Villarreal beat Salzburg 2-1 and Ajax Amsterdam beat Legia Warsaw 1-0.
(Editing by Tony Jimenez)
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