The Uzbek outfit have never advanced past the group stage of the ACL but could seal their progress to the quarter-finals if they beat Al Najaf and second-placed Al Karama of Syria fail to do likewise against Al Sadd in Qatar.
Neftchi will certainly not be lacking in confidence after enjoying a perfect start in their domestic league and opening up a two-point lead in their ACL group with three victories in four matches, including a 1-0 win against Al Najaf in Kuwait City in March.
They continued their impressive form last Friday when they beat Mash’al 3-1, courtesy of a hat-trick by midfielder Akmal Holmatov, for their eight consecutive win in the Uzbek Oliy Liga.
Veteran coach Yuri Sarkisyan, who led Neftchi to the quarter-finals of the Asian Club Championship in 1995, has been further buoyed by the return of strikers Anvar Berdiev and Ilya Kovalenko, who were suspended for the 2-1 win against Al Sadd two weeks ago.
"We managed to beat Al Sadd without two of our key strikers so why should we not be confident of beating Al Najaf with our full squad? We are in good shape because we have no suspensions or injuries," said Sarkisyan, who has coached the club for 20 years.
"But while we are confident of getting a result, we are not over-confident. We realise that Al Najaf have virtually no chance of qualifying for the quarter-finals but they are still a good team and they will not need any extra motivation after our victory against them two months ago."
Sarkisyan is well aware of the situation in Group C and would be more than happy for a helping hand from Al Sadd on Wednesday.
"We would be happy if we beat Al Najaf and we would be even happier if Al Sadd did not lose to Al Karameh because we would be through to the quarter-finals regardless of our result in our final match in Syria," added the Neftchi boss.
"Nefchi have not played in the quarter-finals of an Asian club competition since 1995 so this would be great achievement for our club."
Al Najaf have only one win in four Group C games and face a daunting test in Uzbekistan against an Neftchi side that has won their last four home games in the AFC Champions League.
The Iraqi side warmed up for the match with a 2-1 win last Thursday against Al Forat. The victory, courtesy of goals by Said Mohsen and Aqeel Mohammed, sent Al Najaf through to the second round of the Iraq League
But Al Najaf coach Abdulghani Shahad has injury concerns ahead of the game with defender Ali Abduljabbar ruled out after picking up an injury against Al Forat and forward Foad Jawad also an injury doubt.
Al Najaf will also be sweating on the fitness of defender Haedar Aboudi, midfielder Mohammed Hadi and Yasir Abdulrazaaq, who all nursing injuries.
The team left Iraq on Saturday for Iran before travelling on to Uzbekistan on Monday.